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MENINGOCOCCUS 
MENINGITIS 


BY 

HENRY  HEIMAN,  M.D. 

PROFESSOR   OF    PEDIATRICS,    NEW   YORK    POLYCLINIC   SCHOOL   AND   HOSPITAL  ;     ASSOCIATE 
ATTENDING   PEDIATRIST,    MOUNT   SINAI   HOSPITAL,    NEW   YORK 

AND 

SAMUEL  FELDSTEIN,  M.D. 

LECTURER   ON   PEDIATRICS.  NEW  YORK   POLYCLINIC   SCHOOL  AND  HOSPITAL;    CHIEF   IN  THE 
CHILDREN'S   DEPARTMENT,   MOUNT   SINAI   HOSPITAL   DISPENSARY,   NEW   YORK 

WITH  INTRODUCTION  BY 

HENRY  KOPLIK,  M.D. 

CHIEF  OF  SERVICE,  MOUNT  SINAI   HOSPITAL,    NEW  YORK 


WITH  4  PLATES.  31  FIGURES.  2  IN  COLOR.  AND  4  CHARTS 


PHILADELPHIA  &  LONDON 

J.  B.  LIPPINCOTT  COMPANY 


COPYRIGHT,    1913,    BY  J.    B.   LIPPINCOTT  COMPANY 


PREFACE 

In  the  preparation  of  this  volume  the  aim  of  the 
authors  has  been  to  present  in  compact  form  our 
present  knowledge  of  meningococcus  infection  of  the 
meninges.  As  its  purposes  are  practical  and  it  is 
intended  for  the  use  of  students  and  physicians  en- 
gaged in  clinical  work,  only  so  much  of  technical 
detail  has  been  included  as  can  be  carried  out  with 
ordinary  laboratory  facilities.  We  have  not  deemed 
it  expedient  to  burden  the  volume  with  minute  and 
detailed  laboratory  directions,  which  can  be  of  interest 
only  to  the  special  worker  in  this  field.  The  physician 
at  the  bedside  can  avail  himself  only  of  those  diag- 
nostic and  therapeutic  means  which  are  supplied  to 
him  by  the  equipment  of  the  ordinary  general  hospital. 

In  the  preparation  of  the  volume  a  large  number 
of  authorities  have  been  consulted,  a  number  too 
large  to  be  individually  enumerated  here.  We  must, 
however,  acknowledge  the  invaluable  aid  received 
from  the  perusal  of  the  admirable  monographs  of 
Councilman,  Mallory  and  Wright,  Goeppert,  Busse, 
Elser  and  Huntoon,  and  especially  the  recently  pub- 
lished volume  of  Netter  and  Debre. 

We  have  appended  bibliographic  references  at  the 


iv  PREFACE 

end  of  nearly  every  chapter.  By  a  chronologic  ar- 
rangement, the  historical  advance  in  our  knowledge 
of  each  phase  of  the  subject  is  shown. 

We  take  pleasure  in  acknowledging  our  deep 
gratitude  to  Dr.  Henry  Ivoplik,  attending  pediatrist 
to  the  Mount  Sinai  Hospital,  who  has  generously 
permitted  us  to  make  extensive  use  of  the  valuable 
clinical  material  in  his  wards  at  the  hospital.  We  are 
also  greatly  indebted  to  Dr.  Julius  Rudisch,  Dr. 
Alfred  Meyer,  Dr.  Nathan  E.  Brill,  and  Dr.  Morris 
Manges,  attending  physicians  at  the  Mount  Sinai 
Hospital,  for  permission  to  use  their  clinical  material. 

Dr.  H.  F.  L.  Ziegel  has  kindly  prepared  the 
index. 

We  acknowledge  with  thanks  the  valuable  assist- 
ance given  us  by  Dr.  John  L.  Kantor,  interne  at 
Mount  Sinai  Hospital,  in  the  preparation  of  statisti- 
cal matter. 

We  wish  to  thank  Lea  and  Febiger  for  permission 
to  reproduce  plates  from  Dr.  Koplik's  book. 

For  the  kind  encouragement  and  valuable  sugges- 
tions we  are  indebted  to  our  publishers. 

Henry  Heiman, 
Samuel  Feldstein. 


INTRODUCTION 

This  monograph  is  founded  on  a  study  of  cases 
of  meningococcus  cerebrospinal  meningitis  which 
have  been  treated  in  my  service  in  the  children's  wards 
of  the  Mount  Sinai  Hospital,  New  York,  and  re- 
flects the  methods  of  study  of  symptoms,  diagnosis, 
and  treatment  in  vogue  there.  I  have  been  peculiarly 
fortunate  in  that  the  ages  of  the  patients  treated 
varied  from  earliest  infancy  to  later  childhood.  A 
close  study  of  these  pages  will  show  that  we  have  been 
alive  to  every  advance  in  pathology,  methods  of 
diagnosis,  and  treatment,  and  have  applied  the  latter 
in  a  manner  as  to  give  a  very  definite  idea  as  to  their 
ultimate  value.  Though  the  Flexner  serum  is  a  most 
powerful  weapon  against  this  affection  when  properly 
applied,  much  remains  to  be  done  to  deprive  the 
disease  of  its  terrors.  This  is  particularly  true  of  the 
infection  as  we  see  it  in  infants  of  tender  age  below 
one  year. 

The  mortality  in  these  patients  is  still  not  only 
high,  but  the  maiming  effects  of  the  disease  on  the 
integrity  of  the  general  nervous  system  are  too 
apparent.  The  general  physician  needs  in  his  daily 
work    every    aid    to   the   study   of    symptoms,    their 


vi  INTRODUCTION 

differentiation  and  grouping,  and  an  exposition  of 
the  safest  methods  of  diagnosis  and  treatment.  It  is 
the  object  of  such  a  monograph  as  this  to  give  this 
aid  and  thus  accomplish  a  useful  mission. 

Henry  Koplik,  M.D., 

Chief  of  Service. 
New  York,  October  1,  1913. 


CONTENTS 

CHAPTER  I 

Introduction 1 

Definition;  Terminology ;  History;  Geneva,  1805;  Med- 
field,  1806;  First  Period,  1805-1830;  Second  Period, 
1837-1850;  Third  Period,  1854-1875;  Fourth  Period, 
1876-1882;  Fifth  Period,  1893-1903;  Sixth  Period, 
1904  to  Present  Time. 

CHAPTER  II 

Bacteriology 12 

History;  Staining;  Morphology;  Cultural  Characteristics; 
Growth  on  Plates,  on  Slants,  on  Blood  Agar,  Ascitic 
Broth,  Potato,  Milk;  Conditions  Affecting  Viability 
of  Meningococcus;  Effect  of  Desiccation;  Effect  of 
Light;  Effect  of  Temperature;  Effect  of  Moist  Heat; 
Effect  of  Disinfectant  Solutions;  Fermentation  of 
Carbohydrates;  Agglutination  Reaction;  Absorption 
Tests;  Precipitin  Reaction;  Complement  Fixation 
Reaction;  Action  of  Bile  Salts;  Peritoneal  Reaction; 
Intravenous  Reactions;  Pathogenicity;  Action  on 
Guinea-pigs,  Rabbits,  Dogs,  Goats,  Monkeys;  Differ- 
ence in  Strains;  Gram-negative  Cocci  in  Nasopharynx; 
Parameningococcus. 

CHAPTER  III 

Epidemiology 42 

Unusual  Features;  Small  Morbidity  Rate,  1-2  per  10,000; 
Contagiousness,  Feeble  but  Certain ;  Instances  of  Con- 
tagion; Contagion  in  Hospitals;  Spread  from  One 
Locality  to  Another;  Spread  from  Army  to  Civil  Popu- 
lation; Geographic  Distribution;  Seasonal  Incidence, 


viii  CONTENTS 

Winter  and  Spring;  Age  Incidence,  Children  and 
Young  Adults;  Sex  Incidence;  Race  Incidence;  Influ- 
ence of  Hygienic  Conditions,  Overcrowding;  Condi- 
tion of  the  Patient;  Sporadic  Cases. 

CHAPTER  IV 

Mode  of  Dissemination 55 

Meningococcus  in  Nasopharynx  of  Patients;  Healthy 
Meningococcus  Carriers;  Number  of  Carriers  influ- 
enced by  Period  of  Epidemic,  Season,  and  Intimacy 
of  Patients;  Persistence  of  Meningococcus  in  Naso- 
pharynx; Carriers  in  Individuals  not  Exposed  to  In- 
fections; Distribution  of  the  Meningococcus  in  the 
Respiratory  Tract;  Condition  of  Health  of  Carriers; 
Source  of  Meningococcus  in  Nasopharynx  of  Patients; 
Mode  of  Contagion;  Indirect  through  Agency  of 
Carriers;  High  Degree  of  Receptivity,  Low  Degree  of 
Susceptibility;  Causes  of  Epidemic  Outbreaks;  In- 
crease of  Virulence,  Decrease  of  Resistance;  Mode  of 
Invasion  of  Meningococcus. 

CHAPTER  V 

Pathologic  Anatomy 78 

Anatomical  Features,  Pia,  Arachnoid  and  Dura,  Ven- 
tricles of  Brain,  Cisternal;  Macroscopic  Appearance 
in  Acute  Stage;  Exudate  in  Fulminating  Cases;  Con- 
dition of  Ventricles;  Brain  Tissue  and  Cord;  Chronic 
Stage,  Thickening  and  Adhesions;  Condition  of  Ven- 
tricles; Obliteration  of  Outlets;  Brain  Tissue  and 
Cord;  Microscopic  Lesions,  Acute  Stage;  Purulent 
Infiltration;  Cells  of  Exudate;  Lesions  in  Ventricles; 
Changes  in  Cortex;  Proliferation  of  Neuroglia  and 
Connective  Tissue;  Chronic  Stage;  Organization  of 
Exudate;  Perivascular  Nodes  in  Walls  of  Ventricles; 


CONTENTS  ix 

Degeneration  of  Ganglion-cells;  Lesions  in  Cord; 
Degeneration  of  Nerve-fibres  and  Ganglion-cells; 
Degeneration  of  Posterior  Nerve-roots;  Cranial-nerve 
Lesions;  Meningococcus  in  the  Nervous  System; 
Lesions  in  Other  Parts  of  the  Body;  Upper  Respira- 
tory Tract;  Lower  Respiratory  Tract;  Lymph-nodes ; 
Heart;  Gastro-intestinal  Tract;  Liver;  Spleen;  Kid- 
neys; Joints;  Skin. 

CHAPTER  VI 

Clinical  Types  of  Meningococcus  Meningitis 97 

Ordinary;  Malignant;  Fulminating;  Hyperacute;  Mild; 
Abortive;  Intermittent. 

CHAPTER  VII 

Meningococcus  Meningitis  in  Infancy 106 

Importance;  Frequency;  Difficulties  in  Diagnosis;  Acute 
Onset;  Slight  Rigidity  of  Neck;  Bulging  Fontanelle; 
Macewen  Sign;  Posterior  Basic  Meningitis;  Causative 
Organism;  Pathologic  Anatomy;  Clinical  Course; 
Identity  with  Meningococcus  Meningitis. 

CHAPTER  VIII 

Symptomatology 117 

Pathogenesis;  Mode  of  Onset;  Temperature;  Pulse; 
Respiration;  General  Appearance  and  Attitude;  Men- 
tal Condition;  Ocular  Symptoms;  Changes  in  Pupils; 
Disturbance  of  Ocular  Muscles;  Optic  Nerve  Changes; 
Sensory  Disturbances;  Motor  Disturbances;  Reflexes; 
Vasomotor  and  Trophic  Disturbances;  Rigidity  of 
the  Neck;  Kernig  Sign;  Brudzinski  Neck  and  Leg 
Signs;  Opisthotonus;  Retraction  of  Head;  Rigidity  in 
other  Parts;  Fontanelles  and  Sutures;  Macewen  Sign; 
Gastro-intestinal  Disturbances;  Cutaneous  Manifes- 
tations, Herpes,  Petechia?,  Purpura;  Urine;  Blood; 
Blood-pressure;  Relapses;  Convalescence. 


x  CONTENTS 

CHAPTER  IX 

Cerebrospinal  Fluid 147 

Lumbar  Puncture;  Anatomical  Considerations  and 
Landmarks;  Apparatus;  Technic;  Physiology  of  Cere- 
brospinal Fluid;  Characteristics  of  Normal  Cerebro- 
spinal Fluid;  Cerebrospinal  Fluid  in  Meningococcus 
Meningitis;  Macroscopic  Appearances;  Microscopic 
Appearances;  Cytology;  Bacteriology;  Chemical  Char- 
acters; Changes  in  Cerebrospinal  Fluid  in  the  Course 
of  the  Disease;  Character  of  Cerebrospinal  Fluid  in 
Various  Types  of  the  Disease;  in  Fulminating  Type; 
Mild  Type;  Abortive  Type;  Chronic  Type. 

CHAPTER  X 

Complications  of  Meningococcus  Meningitis 173 

Frequency;  Nervous;  Psychic;  Motor;  Sensory;  Ocular; 
Conjunctivitis;  Conjunctival  Hemorrhages;  Keratitis; 
Iridochoroiditis;  Orbital  Cellulitis;  Disturbance  of 
Extrinsic  Ocular  Muscles;  Disturbances  of  Intrinsic 
Ocular  Muscles;  Amaurosis;  Aural  Complications; 
Otitis  Media;  Deafness;  Pathologic  Anatomy  and 
Pathogenesis;  Clinical  Course;  Visceral  Complica- 
tions; Arthropathy;  Respiratory;  Cardiac;  Digestive; 
Liver;  Geni to-urinary  Tract;  Skin;  Sequelae;  Motor; 
Psychic. 

CHAPTER  XI 

Internal  Hydrocephalus 197 

Pathologic  Anatomy  and  Pathogenesis;  Clinical  Course; 
At  Onset;  After  the  First  Week;  in  Posterior  Basic 
Meningitis. 

CHAPTER  XII 

Diagnosis 207 

Based  on  History,  Clinical  Course,  and  Laboratory 
Examination;  Sources  of  Diagnostic  Error;  Absence 


CONTENTS  xi 

of  Characteristic  Symptoms;  Prominence  of  Symp- 
toms; Characteristic  of  Other  Diseases;  Apyrexia; 
Mild  Psychic  Disturbances;  Absence  of  Characteristic 
Rigidity  and  Kernig  Sign;  Intermittent  Temperature; 
Cutaneous  Eruptions;  Digestive  Disturbances;  Arth- 
ropathy. 

CHAPTER  XIII 

Differential  Diagnosis 213 

Pneumonia;  Typhoid;  Typhus;  Influenza;  Septicopye- 
mia; Tetanus;  Poliomyelitis;  Polioencephalitis;  Men- 
ingism;  Meningeal  Hemorrhages;  Gastro-enteritis; 
Infantile  Eclampsia;  Tetany;  Tuberculous  Meningitis; 
Acute  Suppurative  Meningitides;  Aseptic  Meningitis. 

CHAPTER  XIV 

Laboratory  Diagnosis 224 

Cerebrospinal  Fluid;  Microscopic  Appearance;  Fibrin 
Content;  Protein  Content;  Reduction  of  Potassium 
Permanganate;  Cytology;  Bacteriology;  Precipito- 
reaction  of  Vincent  and  Bellot;  Blood;  Agglutination; 
Opsonic  Index;  Complement  Deviation;  Meningo- 
coccus in  Blood;  Meningococcus  in  Nasopharynx. 

CHAPTER  XV 

Prognosis 237 

Prognosis  in  Epidemic  and  Sporadic  Forms;  Individual 
Prognosis;  Factors  Influencing  the  Prognosis;  Age; 
Grave  Symptoms;  Prognosis  as  to  Complete  Recovery. 

CHAPTER  XVI 

Treatment 243 

History;  Serum  Treatment;  Preparation  of  Serum; 
Flexner;  Kolle  and  Wassermann;  Jochmann;  Dopter; 
Manner  of  Therapeutic  Action;  Bacteriolysins;  Bac- 


xii  CONTENTS 

teriotropins;  Anti-endotoxins ;  Standardizations  of 
Serum;  Basic  Principles  of  Serotherapy;  Technic  of 
Serum  Administration;  Systematic  Treatment;  intra- 
ventricular injections;  Technic;  Dosage;  Results  of 
Serum  Treatment;  Effect  on  Mortality;  Effect  on 
Symptoms;  Effect  on  Cerebrospinal  Fluid;  Microsco- 
pic; Protein  Contents;  Cytology;  Bacteriology;  Re- 
lapses; Effect  on  Duration;  Effect  on  Complications; 
Sequelae;  Serum  Disease;  Untoward  Results;  Causes 
of  Failure;  Symptomatic  Treatment;  Lumbar  Punc- 
ture; Passive  Hypersemia  (Bier);  Hot  Baths;  Drug 
Therapy;  General  Management;  Prophylaxis;  Pro- 
phylactic Vaccination. 


ILLUSTRATIONS 

PLATES 

PAGE 

I.  Macroscopic  Lesions  of  Convexity  of  Brain  Meningococcus  Men- 
ingitis       80 

II.  Side  View  of  Brain  Meningococcus  Meningitis 81 

III.  Lesions  of  Spinal  Cord  Meningococcus  Meningitis,  Adult  Case.     (In 

color.) 86 

IV.  Posterior  Basic  Meningitis,  Child  Six  Months  of  Age 110 

FIGURES 

1.  Cerebrospinal  Exudate 16 

2.  Pure  Culture  of  Meningococcus  18  Hours  Old 17 

3.  Pure  Culture  of  Meningococcus  48  Hours  Old 17 

4.  Pure  Culture  of  Meningococcus  72  Hours  Old 17 

5.  Colony  of  Meningococcus 20 

6.  Plate  Culture  of  Meningococcus 20 

7.  Slant  Culture  of  Meningococcus 21 

8.  Showing  Membranes  Covering  Brain  and  Location  of  Cisterna 7S 

9.  Showing  Ventricular  System  of  Brain  and  Foramina  of  Fourth  Ven- 

tricle    80 

10.  Posterior  Basic  Meningitis,  Age  Eleven  Months Ill 

11.  Epidemic  Cerebrospinal  Meningitis.    Ordinary  Temperature  Curve.  . .  121 

12.  Intermittent  Temperature  Curve 122 

13.  Babinski  Sign 130 

14.  15.  Kernig  Sign 132 

16.  Brudzinski  Signs 133 

17.  Anatomical  Landmarks  for  Lumbar  Puncture 151 

18.  Cannula,  Guard,  Stilette,  Conus;  Rubber  Tubing,  Manometer  Tube.  .   153 

19.  Kroenig's  Lumbar  Puncture  Apparatus 154 

20.  Crohn's  Apparatus  for  Estimation  of  Pressure  in  Cerebrospinal  System.   155 

21.  Position  of  Patient  with  the  Needle  Introduced  into  the  Cerebrospinal 

Canal 156 

22.  Showing  Direction  of  Needle 157 

23.  Spinal  Veins  in  a  Horizontal  Section  Viewed  from  Above.    (In  color.)    157 

2t.  Measuring  the  Pressure 159 

25.  Estimation  of  Pressure  of  Cerebrospinal  Fluid  by  Means  of  Quincke's 

Manometer 158 

xiii 


xiv  ILLUSTRATIONS 

26.  Introduction  of  Antimeningitis  Serum  into  the  Spinal  Canal  by  Means 

of  Funnel 158 

27.  Catalepsy  Complicating  Cerebrospinal    Meningitis;  Age  Six  Years.  ..  .  174 

28.  Cytology  of  Epidemic  Cerebrospinal  and  Tuberculous  Meningitis 228 

29.  Apparatus  for  Administration  of  Antimeningitis  Serum 258 

30.  Intraventricular  Puncture  and  Injection  of  Serum  in  an  Infant 272 

SI.  Direction  of  Needle  for  Intraventricular  Puncture  and  Injection  of 

Serum 272 

CHARTS 

I.  Rise   or   Fall   in   the   Temperature    Apparently    Due    to   Lumbar 

Puncture 122 

II.  Critical  Fall  in  the  Temperature  Caused  by  Serum  Injections 144 

III.  Repetition  of  Lumbar  Puncture  after  an  Interval  of  Five  Days  to 

ward  off  a  Possible  Relapse 266 

IV.  Fever  Charts  of  so-called  Fast  Cases  of  Meningococcus  Meningitis.  .   293 


MENINGOCOCCUS 
MENINGITIS 

CHAPTER  I 

Introduction 

Definition. — Meningococcus  meningitis  is  an  in- 
fectious, slightly  contagious  disease,  which  occurs 
sporadically  and  in  epidemics,  due  to  the  presence, 
in  the  meninges  of  the  brain  and  spinal  cord,  of  the 
meningococcus  (diplococcus  intracellularis  meningi- 
tidis), and  characterized  by  a  number  of  constitu- 
tional and  local  symptoms  of  great  variability  and 
irregularity. 

Terminology. — In  the  extensive  literature  the 
disease  has  received  a  great  number  of  names,  such  as 
spotted  fever,  spotted  typhus,  black  fever,  exanthe- 
matic  typhus,  brain  fever,  petechial  fever,  epidemic 
cephalalgia,  and  cerebrospinal  fever.  The  term  most 
commonly  employed  is  that  of  epidemic  cerebrospinal 
meningitis.  But  its  inadequacy  becomes  evident 
when  we  consider  the  great  number  of  sporadic  cases 
which  are  seen  in  all  the  large  cities.  The  specific 
nature  of  the  disease  having  become  firmly  estab- 
lished, an  etiologic  designation  is  the  only  adequate 
i  1 


2  MENINGOCOCCUS  MENINGITIS 

and  proper   term.     It  includes   all   forms   and  ex- 
cludes none. 

It  is  probable  that  epidemics  of  meningitis  may 
also  be  caused  by  the  pneumococcus  and  the  strepto- 
coccus mucosus  (Bonome),  but  it  is  safe  to  say  that 
the  vast  majority  of  epidemics  recorded  in  the  litera- 
ture have  resulted  from  infection  by  the  meningo- 
coccus. 

History. — The  dim  history  of  this  disease  begins 
in  the  Middle  Ages.  Many  epidemics  are  mentioned 
in  the  literature  in  which  symptoms  very  suggestive 
of  meningitis  were  present.  But,  as  autopsies  were 
rarely  performed,  it  is  impossible  to  be  certain  that 
the  disease  was  meningitis.  They  were  described 
under  phrenitis,  petechial  fever,  cerebral  fever,  and 
epidemic  cephalalgia. 

The  accepted  history  of  meningococcus  meningi- 
tis begins  at  Geneva  in  1805.  The  epidemic  started 
in  February  on  the  left  bank  of  Lake  Geneva,  and 
lasted  during  March  and  April.  Thirty-three  per- 
sons died  of  the  disease,  but  there  were  no  cases  of 
contagion  at  the  hospital,  and  the  commission  ap- 
pointed by  the  Government  did  not  consider  it  de- 
serving of  being  called  an  epidemic.  The  disease  was 
described  as  follows  by  Vieusseux  (quoted  from 
Netter  and  Debre)  : 

"  It  began  suddenly  with  extreme  prostration ;  the 


INTRODUCTION  3 

face  was  drawn ;  the  pulse  feeble,  small,  and  frequent, 
sometimes  it  could  hardly  be  felt;  hard  and  bounding 
in  a  small  number  of  cases.  There  was  violent  head- 
ache, especially  frontal.  Then  there  appeared  pre- 
cordial pain  or  vomiting  of  bilious  matter,  rigidity  of 
the  spine,  and  convulsions  in  infants.  .  .  .  The  body 
presented  livid  spots,  especially  after  death,  some- 
times even  during  life." 

The  pathological  description  was  given  as  follows 
by  Mathey: 

"  The  meningeal  vessels  were  markedly  congested. 
A  gelatinous  blood-stained  fluid  covered  the  whole 
surface  of  the  brain.  There  was  fluid  in  the  ventri- 
cles. The  choroid  plexus  was  a  deep  red.  A  yellow 
puriform  exudate  was  seen  on  the  posterior  aspect 
of  the  cerebral  lobes  and  in  the  interior.  There  was 
no  manifest  change  in  the  cerebral  tissue.  The  same 
exudate  was  found  along  the  optic  nerves,  the  base 
of  the  cerebellum,  and  the  vertebral  canal." 

In  the  United  States  the  disease  was  first  seen  in 
epidemic  form  in  Medfield,  Mass.,  during  March, 
1806.  It  was  described  by  Danielson  and  Mann  in  a 
contribution  to  the  Medical  and  Agricultural  Regis- 
ter, bearing  the  title,  "  A  Singular  and  Very  Fatal 
Disease  which  Lately  made  its  Appearance  in  Med- 
field, Mass."    On  account  of  the  remarkable  descrip- 


4  MENINGOCOCCUS  MENINGITIS 

tion  of  the  disease  given  by  these  authors,  a  part  of 
the  paper  is  worth  quoting: 

"  Without  any  apparent  predisposition,  the  pa- 
tient is  suddenly  taken  with  violent  pain  in  the  head 
and  stomach,  succeeded  by  cold  chills  and  followed 
by  nausea  and  vomiting;  matter  discharged  from 
stomach  of  no  unusual  or  morbid  appearance;  re- 
spiration short  and  laborious  .  .  .  the  eyes  have  a 
wild  vacant  stare  without  much,  if  any,  appearance 
of  inflammation  .  .  .  these  symptoms  are  accom- 
panied by  a  peculiar  fearfulness,  as  if  in  danger  of 
falling  from  the  bed  or  the  nurse's  arms,  and  con- 
tinue from  six  to  nine  hours,  when  coma  commences, 
with  increasing  debility ;  extremities  become  cold ;  livid 
spots  resembling  petechia?  appear  under  the  skin,  on 
the  face,  neck,  and  extremities;  pulse  small,  irregu- 
lar, and  unequal;  spasms  occur  at  intervals,  which 
increase  in  violence  and  frequency  in  proportion  as 
the  force  of  the  circulation  decreases ;  at  this  time  the 
eyes  appear  glassy,  and  the  size  of  the  pupils  varies 
suddenly,  from  almost  obliterating  the  iris  down  to 
the  size  of  a  millet-seed,  and  then  again  as  suddenly 
dilating.  These  symptoms  seem  to  mark  the  second 
period  of  the  disease  and  continue  from  three  to  five 
hours.  The  third  and  last  stage  is  distinguished  by  a 
total  loss  of  pulsation  at  the  wrists;  livid  appear- 
ances become  more  general;  spasms  more  violent; 


INTRODUCTION  5 

coma  more  profound;  death!  The  patient  has,  in 
general,  continued  in  the  last  stage  from  six  to 
twelve  hours." 

On  post-mortem  examination,  serous  effusion  was 
found  between  the  membranes,  which  adhered  to  each 
other  and  to  the  brain  in  several  places;  congestion 
and  softening  of  the  brain. 

The  best  and  most  classical  history  of  the  disease 
is  given  by  Hirsch  in  his  well-known  treatise  on 
"  Historisch-Geographische  Pathologie,"  to  which 
the  reader  interested  in  this  phase  of  the  subject  is 
referred.    He  divides  its  history  into  four  periods : 

1.  1805-1830,  during  which  the  disease  was 
general  in  the  United  States.  In  Europe  it  occurred 
in  isolated  epidemics. 

2.  1837-1850.  During  this  period  there  were 
wide-spread  epidemics  in  France,  Italy,  Algiers,  the 
United  States,  and  Denmark. 

3.  1854-1875.  In  this  period  the  disease  was 
widely  diffused  throughout  most  of  Europe,  the  ad- 
joining countries  of  Western  Asia,  the  United  States, 
and  parts  of  Africa  and  South  America. 

4.  1870-1882.  During  this  period  there  were 
isolated  epidemic  outbreaks.  We  may  add  a  fifth  and 
sixth  period—  from  1893  to  1903,  and  from  1904  to 
the  present  time.    In  these  periods  there  were  exten- 


6  MENINGOCOCCUS  MENINGITIS 

sive  epidemics  in  the  United  States,  Portugal,  Ger- 
many, England,  and  France. 

The  following  brief  historical  account  is  based  on 
the  studies  of  Hirsch  and  Jacobi. 

The  First  Period  (1805-1830).— During  the 
first  period  the  disease  was  epidemic  not  only  in  Med- 
field  but  also  in  New  Hampshire,  Connecticut,  New 
Jersey,  Vermont,  Virginia,  Kentucky,  Ohio,  New 
York,  Pennsylvania,  and  Maine.  From  1814  to  1816 
epidemics  occurred  in  all  the  New  England  States. 
From  1816  to  1823  no  severe  epidemics  were  ob- 
served. In  1823  there  was  an  epidemic  outbreak  in 
Middletown,  Conn.  The  epidemic  in  Trumbull, 
Ohio,  in  1828,  closed  the  first  period  in  the  United 
States.  Three  important  contributions  to  the  Ameri- 
can literature  of  the  disease  were  made  in  this  period : 
the  paper  by  Danielson  and  Mann,  already  men- 
tioned; the  communication  by  a  committee  of  the 
Massachusetts  Medical  Society  (consisting  of  James 
Jackson,  Thomas  Welch,  and  J.  C.  Warren)  ;  and 
the  classical  book  by  Elisha  North  entitled,  "  A 
Treatise  on  a  Malignant  Epidemic  Commonly  Called 
Spotted  Fever."  The  epidemics  were  characterized 
by  various  eruptions  and  by  the  occurrence  of  pul- 
monary complications. 

In  Europe  the  disease  prevailed  in  Brianca,  Dan- 
zig, Brest,  Paris,  and  Metz.    The  frequency  of  erup- 


INTRODUCTION  7 

tions  and  respiratory  complications  was  noted  here 
also. 

The  Second  Period  ( 1837-1850)  .—In  the  United 
States  the  disease  was  wide-spread  from  1842  to 
1850.  In  1842  Rutherford  County,  Tennessee,  and 
Montgomery,  Alabama,  were  visited  by  the  epidemic. 
In  1845  an  epidemic  occurred  in  Mt.  Vernon,  Illinois. 
It  prevailed  in  Arkansas,  Vicksburg,  Mississippi, 
Tennessee,  and  Missouri  in  1846-1847.  Mont- 
gomery, Alabama,  was  visited  for  the  second  time 
in  1848.  In  the  same  year  the  disease  prevailed  in 
Pennsylvania  and  Worcester,  Mass.  The  negro 
quarters  of  New  Orleans  were  invaded  in  1850. 

In  Europe  the  most  wide-spread  epidemic  during 
this  period  occurred  in  France.  It  began  in  the 
south  of  France  and  spread  for  the  next  ten  years 
from  the  southwest  to  the  northeast.  By  the  move- 
ments of  the  18th  Regiment  the  disease  was  carried 
from  the  Landes  to  Rochefort,  Versailles,  Chartres, 
Metz,  Nancy,  Strassburg,  Schlestadt,  and  Colmar. 
It  affected  chiefly  the  military  population.  The 
epidemic  was  transported  to  Algeria  and  Italy.  From 
1839  to  1845  wide-spread  epidemics  occurred  in 
Italy.  Epidemics  were  also  seen  in  Corfu,  Gibraltar, 
Denmark,  and  Ireland.  In  this  period  the  clinical 
features  of  the  disease  were  carefully  studied  and  de- 


8  MENINGOCOCCUS  MENINGITIS 

scribed  by  the  French  clinicians  (Lespes,  Tourdes 
and  Faure-Villars,  etc. ) . 

The  Third  Period  (1854-1875).— In  the  United 
States  there  was  subsidence  of  the  disease  from  1850 
to  1856.  Then  new  outbreaks  occurred  during  1856 
and  1857  in  Salisbury,  North  Carolina,  and  the 
western  part  of  New  York  State.  The  disease  pre- 
vailed in  the  Army  of  the  Potomac  in  the  winter  of 
1861-1862.  In  1862-1863  it  invaded  the  army  camp 
around  Newbern,  N.  C.  It  reappeared  in  Massa- 
chusetts in  1864-1865.  Philadelphia  had  an  epidemic 
in  1863-1866.  During  the  same  period  it  was  preva- 
lent in  Indiana  and  Iowa,  among  the  Confederate 
troops  at  Norfolk,  Va.,  at  the  military  school  in  New- 
port, R.  I.,  Mobile,  Alabama,  Illinois,  New  Jersey, 
Vermont,  Connecticut,  and  Ohio.  In  1869-1870 
meningococcus  meningitis  was  seen  in  Alabama, 
Pennsylvania,  New  Jersey,  New  York  City  and 
Brooklyn,  Illinois,  South  Carolina,  and  the  port  of 
Georgia.  Massachusetts,  Indiana,  and  Michigan 
were  visited  by  epidemics  in  1873.  In  Boston  the 
epidemic  occurred  in  1874. 

From  1854  to  1861  extensive  epidemics  occurred 
throughout  the  whole  of  the  Scandinavian  Peninsula, 
affecting  Sweden  more  severely  than  Norway.  The 
disease  advanced  from  the  south  to  the  northwest, 
beginning  each  winter  where  it  had  stopped  the  previ- 


INTRODUCTION  9 

ous  summer.  It  caused  4158  deaths  in  seven  years. 
Southern  and  central  Germany  was  invaded  during 
1863-1866.  Epidemics  were  also  seen  at  this  time  in 
Austria,  Hungary,  and  Russia.  The  disease  was 
epidemic  in  Ireland  from  1865  to  1868. 

The  Fourth  Period  (1876-1882.— In  this  period 
no  very  extensive  epidemics  are  recorded,  but  the 
disease  prevailed  in  the  form  of  localized  epidemics 
in  France,  Italy,  Germany,  Austria,  and  Scandinavia. 
There  are  no  records  of  epidemics  in  the  United 
States. 

The  Fifth  Period  (1893-1903).— In  1893  an  ex- 
tensive epidemic  occurred  in  New  York  City,  which 
was  described  by  Berg.  In  the  same  year  the  disease 
appeared  in  the  Lonaconing  Valley  in  Maryland,  and 
was  carefully  studied  by  Flexner  and  Barker.  The 
epidemic  in  Massachusetts  during  1897-1898  gave 
rise  to  the  admirable  contribution  by  Councilman, 
Mallory  and  Wright. 

During  this  period  epidemics  were  seen  in  France, 
Germany,  Austria,  Norway,  Scotland,  Ireland,  Bos- 
nia, Italy,  and  Algeria.  The  severe  epidemic  in 
Portugal  during  1901-1903  gave  rise  to  a  valuable 
contribution  by  Bettencourt  and  Franca.  In  this 
period  the  bacteriology  of  the  disease  became  estab- 
lished on  a  firm  basis. 

The    Sixth    Period    (1904-         ).— The    disease 


10        MENINGOCOCCUS  MENINGITIS 

prevailed  in  New  York  during  1904  and  1905.  In 
1905  there  were  2755  cases.  There  was  a  severe 
epidemic  in  Prussia  from  1905  to  1907.  The 
provinces  chiefly  affected  were  Silesia  and  West- 
phalia. In  Great  Britain  severe  epidemics  were 
present  in  Glasgow,  Edinburgh,  and  Belfast.  Dur- 
ing 1908-1910  an  extensive  epidemic  was  seen  in 
France.  During  1910  a  severe  epidemic  occurred 
along  the  Pacific  Coast.  In  1911  the  disease  spread 
to  the  Southwestern  States,  affecting  chiefly  Texas 
and  Louisiana. 

The  extensive  researches  undertaken  during  this 
period  have  shown  the  importance  of  the  germ  carriers 
in  the  spread  of  the  disease.  In  this  period  the  culmi- 
nation of  the  practical  study  of  the  disease  was 
reached  when  the  serum  treatment  was  developed. 

Bibliography. 

Viesseux:    Jour.  gen.  de  Med.,  1806,  xi,  163. 

Mathey :   Jour.  gen.  de  Med.,  1806,  xi,  243. 

Danielson  and  Mann :    Med.  and  Agricultural  Register,  1806, 

i,  65. 
North:     A  Treatise  on   a  Malignant  Epidemic   Commonly 

•called  Spotted  Fever,  New  York,  1811. 
Jackson,  Welch,  and  Warren :    Report  of  Committee  to  Mass. 

Med.  Soc,  Med.  Communications,  1813. 
Tourdes :    Histoire  de  l'epidemic  de  Meningite  cerebrospinal 

observee  a  Strassbourg  en  1840  et  1841,  Strassburg,  1842. 


INTRODUCTION  11 

Frothingham:    Amer.  Med.  Times,  1864,  viii,  207. 
Niemeyer:     Die  epidemische  Cerebrospinalmeningitis,  Berlin, 

1865. 

Webber:    Boston  Med.  and  Surg.  Jour.,  1866,  lxxv,  29. 
Hirsch :   Die   Meningitis   Cerebrospinal    epidemica,   Berlin, 

1866. 
Upham :     Boston  Med.  and  Surg.  Journal,  1867,  lxxvi,  485. 
Stille:     Epidemic  Meningitis,  Phila.,  1867. 
Clymes :     Epidemic  Cerebrospinal  Disease,  Phila.,  1872. 
Upham:    Boston  Med.  and  Surg.  Jour.,  1874,  xci,  221. 
Hirsch:      Historisch-Geographischc   Pathologic,    Stuttgart, 

1886,  2Aufl.,iii. 
Flexner    and    Barker:      Amer.    Jour.    Med.    Sciences,    1894, 

cvii,  155. 
Berg:     Archives  Pediatrics,  1894,  xi,  352. 
Jaeger:       Die     cerebrospinalmeningitis     als     Heeresseuche, 

Bibliothek  Coler,  Berlin,  1901. 
Chapin:     Med.  News,  1904,  lxxxiv,  1063. 
Jacobi :       Transactions    Med.    Soc.    State    of    New    York, 

1905,  89. 
Netter    and    Debre:     La    Meningite     Cerebrospinal,  Paris, 

1911. 


CHAPTER  II 

Bacteriology 

History. — In  1884  Marchiafava  and  Celli  found 
at  autopsy,  in  two  cases  of  epidemic  meningitis,  oval 
micrococci  within  the  protoplasm  of  leucocytes  and 
endothelial  cells.  As  no  cultures  were  made,  and  the 
result  of  staining  by  Gram  method  is  not  mentioned, 
it  can  only  be  surmised,  but  not  proved,  that  these 
observers  were  dealing  with  the  meningococcus. 
Leichtenstern,  in  1885,  during  an  epidemic  at 
Cologne,  comprising  41  cases,  saw,  on  microscopic 
examination  of  9  cases,  intracellular  diplococci,  cul- 
tures of  which  yielded  a  number  of  bacilli,  and  cocci 
which,  although  of  the  same  shape,  varied  markedly 
in  size.  Schwabach,  as  quoted  by  Councilman, 
Mallory  and  Wright,  also  found  diplococci  in  the  pus- 
cells  of  the  discharge  from  the  ear  in  a  case  of  otitis 
media  secondary  to  meningitis.  Previous  to  this  time 
the  only  identifiable  organism  found  in  the  meningeal 
exudate  was  the  diplococcus  pneumonia?.  Practically 
all  authors  of  this  period,  including  Weichselbaum, 
were  of  the  opinion  that  the  pneumococcus  was  the 
only  organism  capable  of  producing  a  primary 
meningitis. 

In  1887,  however,  Weichselbaum  found,  in  the 

12 


BACTERIOLOGY  13 

meningeal  exudate  and  ventricular  fluid  of  6  out  of  8 
cases  of  primary  apparently  sporadic  cases  of 
meningitis,  an  organism  clearly  not  the  pneumo- 
coccus  and  which  he  named  diplococcus  intracellu- 
laris  meningitidis.  It  was  a  Gram-negative  diplo- 
coccus occurring  partly  within  and  partly  outside  the 
pus-cells.  Culturally  it  was  shown  to  be  an  obligatory 
aerobe,  whose  optimum  growth  temperature  was 
37°  C.  It  grew  best  on  media  containing  animal 
proteids  and  required  transplantation  every  day  or 
second  day.  It  possessed  feeble  pathogenic  powers, 
but  direct  inoculation  in  the  meninges  of  dogs  pro- 
duced meningitis  and  encephalitis.  Since  in  the  other 
two  of  the  eight  cases  Weichselbaum  found  the 
pneumococcus,  he  expressed  the  guarded  opinion  that 
both  of  these  organisms  might  produce  a  primary 
meningitis.  Moreover,  as  at  that  time,  to  his  knowl- 
edge, there  was  no  epidemic  of  meningitis  in  Vienna, 
he  did  not  feel  justified  in  claiming  an  important 
role  for  this  diplococcus  in  the  causation  of  epidemic 
meningitis. 

Though  his  painstaking  studies  were  confirmed 
by  Goldschmidt  in  the  same  year  and  by  Edler  soon 
thereafter,  the  discovery  aroused  but  slight  interest 
and  was  soon  almost  wholly  forgotten. 

Isolated  finding  of  the  meningococcus  was  reported 
now  and  then.    Weichselbaum,  however,  despite  un- 


14         MENINGOCOCCUS  MENINGITIS 

remitting  search,  did  not  meet  with  this  organism 
again  until  1895.  By  this  time  the  clinical  study  of 
meningitis  had  been  immeasurably  advanced  by 
Quincke's  announcement  in  1891  of  his  method  of 
obtaining  cerebrospinal  fluid  in  the  living  by  lumbar 
puncture. 

In  1895  Jaeger,  while  studying  a  small  epidemic 
at  a  garrison  in  Stuttgart,  found  in  14  cases  at 
autopsy  an  organism  which  he  identified  with  the 
Weichselbaum  diplococcus.  It  was  partly  intra- 
cellular, being  found  at  times  within  the  nuclei.  While 
Gram-negative  in  sections,  it  stained  by  Gram  in  the 
exudates  and  cultures.  It  grew  well  on  agar,  glycerin 
agar,  and  bouillon  at  temperatures  ranging  between 
22°  and  37°  C,  and  showed  considerable  resistance 
to  external  influences.  Chains  of  from  twenty  to 
thirty  individuals  were  seen  in  two  cultures.  At 
times  a  capsule  was  demonstrable.  Despite  the  ob- 
vious morphologic  and  cultural  differences  between 
this  organism  and  the  diplococcus  described  so  care- 
fully by  Weichselbaum,  Jaeger  identified  the  two,  and 
claimed  that  this  diplococcus,  and  not  the  pneumo- 
coccus,  as  had  been  generally  accepted  up  to  this  time, 
was  the  sole  infective  agent  of  epidemic  cerebro- 
spinal meningitis.  His  publication,  unlike  that  of 
Weichselbaum,  aroused  great  interest,  and  in  the  sue- 


BACTERIOLOGY  15 

ceeding  years  many  apparent  confirmations  of  his 
observation  were  reported. 

Heubner,  in  1896,  found,  in  the  lumbar-puncture 
fluid  of  two  cases,  a  diplococcus  which  presented  all 
the  characteristics  described  by  Weichselbaum.  In 
three  other  cases,  however,  he  demonstrated  the 
presence  of  a  Gram-positive  diplococcus  which 
formed  chains  and  grew  at  room  temperature.  By 
injecting  this  organism  in  the  spinal  canal  of  a  goat, 
he  produced  acute  meningitis. 

A  period  of  great  confusion  followed.  Some  con- 
firmed Weichselbaum's  observations,  others  those  of 
Jaeger,  while  still  others  attempted  to  identify  the 
meningococcus  with  the  pneumococcus.  Soon  there- 
after the  view  became  quite  prevalent  that  there  were 
two  types  of  the  meningococcus,  the  Weichselbaum 
type  and  the  Jaeger-Heubner  type.  Considerable 
light  was  thrown  on  this  phase  of  the  meningitis  ques- 
tion by  the  extensive  studies  of  Councilman,  Mallory 
and  Wright  (111  cases,  55  lumbar  punctures,  and  35 
autopsies),  Faber  (60  cases),  Albrecht  and  Ghon 
(30  cases),  and  Bettencourt  and  Franca  (271  cases). 
The  more  recent  studies  during  the  large  epidemics 
in  Germany,  America,  England,  and  France,  aided 
as  they  were  by  the  development  of  the  fermentation 
test  and  the  modern  serum  reactions,  have  shown 
conclusively  the  untenability  of  the  contentions  of 


16         MENINGOCOCCUS  MENINGITIS 

Jaeger  and  his  followers,  and  completely  established 
the  constancy  of  those  characteristics  of  the  organism 
originally  described  by  Weichselbaum.  An  explana- 
tion for  the  strange  results  obtained  by  the  Jaeger 
school  was  found  in  the  difficulties  surrounding  the 
growth  of  the  meningococcus  on  artificial  media  and 
the  ease  with  which  other  organisms  that  grow  under 
less  exacting  conditions  contaminate  the  media  em- 
ployed for  its  cultivation.  In  animal  experiments 
the  ready  invasion  of  more  resistant  secondary  micro- 
organisms was  another  frequent  source  of  error.  By 
his  studies  of  the  morphological,  cultural,  fermenta- 
tive, and  agglutinating  properties  of  the  two  diplo- 
cocci,  v.  Lingelsheim  has  shown  that  they  can  not  be 
considered  to  belong  to  the  same  species.  To  avoid 
confusion  in  the  future,  he  prefers  to  call  the  Jaeger 
coccus,  diplococcus  crassus. 

The  following  account  of  the  bacteriologic  fea- 
tures of  the  meningococcus  is  based  in  part  on  the 
admirable  paper  of  Elser  and  Huntoon. 

Staining. — All  the  ordinary  aniline  dyes  stain  the 
meningococcus  with  great  ease.  It  is  now  well  estab- 
lished that  the  meningococcus  is  invariably  Gram- 
negative,  i.e.,  it  takes  the  counterstain.  This  staining 
characteristic  of  the  meningococcus  is  of  great  diag- 
nostic importance,  as  it  offers  a  quick  and  reliable 
method  of  identification  of  this  organism  in  the  cere- 


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BACTERIOLOGY  17 

brospinal  fluid.  The  Neisser  stain  frequently  shows 
the  presence  of  metachromatic  granules  which  are 
microchemically  identical  with  the  Babes-Ernst 
bodies.  The  number  and  size  of  these  granules  vary 
with  the  strain  of  the  organism,  its  age,  and  the 
culture-medium  on  which  it  grows.  When  grown  on 
glucose  ascitic  agar  at  36°  C,  the  granules  begin  to 
appear  after  six  hours,  and  attain  their  maximum 
size  within  eighteen  hours.  They  disappear  com- 
pletely after  a  short  exposure  to  room  temperature, 
or  after  more  than  a  week's  growth  on  an  artificial 
medium. 

Morphology  ( Fig.  1 ) . — The  typical  form  of  the 
meningococcus  is  that  of  two  hemi-ellipses  apposed 
by  their  flat  surfaces  and  separated  from  each  other 
by  a  linear  space.  While  the  double  coccus  is  the 
predominant  form,  tetrads  and  small  groups  of  diplo- 
cocci  are  not  infrequent.  Isolated  single  cocci  occur 
more  rarely.  The  meningococcus  shows  no  distinct 
capsule.  At  times  a  mucinous  envelope  is  seen,  which 
has  been  mistaken  by  some  observers  for  a  capsule. 
It  may  also  be  surrounded  by  an  unstained  zone 
which  is  due  to  contraction  of  the  cell  envelope  or  re- 
traction of  the  culture-medium. 

In  the  exudate  obtained  by  lumbar  puncture,  the 
diplococci  are  often  found  within  the  protoplasm  of 
the  leucocytes.    At  times  these  are  completely  filled 


18         MENINGOCOCCUS  MENINGITIS 

with  meningococci.  The  relative  number  of  intra- 
and  extracellular  organisms  varies  with  different 
specimens  of  cerebrospinal  exudate,  and  seems 
partly  dependent  on  a  difference  in  the  strains  of  the 
organism.  Following  the  injection  of  serum,  the 
organisms,  if  at  all  demonstrable,  are  very  frequently 
confined  to  the  protoplasm  of  the  leucocytes.  The 
phagocytic  cells  may  be  normal  or  degenerated. 

Lack  of  uniformity  as  regards  size,  shape,  and 
staining  is  a  striking  characteristic  of  this  organism. 
Polymorphism  is  usually  marked  in  smears  from  the 
nasopharynx  and  still  more  in  those  derived  from 
cultures.  In  vigorous  young  cultures  (sixteen  to 
twenty-four  hours  old)  most  of  the  organisms  stain 
sharply  and  uniformly.  In  cultures  twenty-four  to 
forty-eight  hours  old,  four  forms  are  seen: 

1.  Predominantly  well-stained  diplococci  and 
tetrads. 

2.  Intensely  stained  cocci,  normal  in  size  and 
shape   (resistant  forms). 

3.  Less  deeply  stained  normal  cocci. 

4.  Intensely  stained  giant  forms  which  are  from 
four  to  five  times  as  large  as  the  ordinary  cocci  (Figs. 
2,  3,  and  4).  The  last  two  are  involution  or  de- 
generation forms.  These  disappear  rapidly  in  oldei 
cultures.    As  degeneration  progresses,  the  cocci  firsi 


BACTERIOLOGY  19 

fail  to  stain,  later  they  become  disintegrated,  and 
finally  unstained  detritus  alone  is  left. 

Flexner  has  shown  that  this  process  is  due  to  the 
action  of  an  enzyme,  which  is  present  in  the  cell  bodies 
of  the  meningococci.  Soon  after  the  death  of  the 
organism  the  enzyme  begins  to  dissolve  the  cell 
envelope.  When  the  meningococcus  is  killed  at  60° 
C,  disintegration  proceeds  rapidly,  as  the  enzyme  is 
not  affected  by  this  temperature.  Killed  at  65"  to  70° 
C.  there  is  no  disintegration,  as  the  enzyme  is  also 
destroyed  by  this  temperature.  A  similar  action  is 
exhibited  by  potassium  cyanide,  which  kills  the  organ- 
isms and  also  inhibits  the  action  of  the  enzyme.  This 
enzyme  is  also  capable  of  disintegrating  other  germs 
such  as  bacillus  coli,  typhoid  bacillus,  pyocyaneus, 
staphylococcus,  and  micrococcus  catarrhalis.  The 
meningococcus  never  occurs  in  long  chains.  This  is 
another  important  characteristic  that  separates  it 
from  the  Jaeger  coccus.  Even  short  chains  of  four 
to  six  individuals  are  very  rarely  seen.  The  presence 
of  chains  in  a  culture  is  therefore  presumptive  evi- 
dence that  the  organism  in  question  is  not  the  true 
meningococcus. 

Cultural  Characteristics. — The  meningococcus  is 
one  of  the  most  difficult  organisms  to  grow  on  artifi- 
cial media.  It  makes  exacting  demands  as  regards 
the    composition    and    reaction    of    the    medium,    the 


20         MENINGOCOCCUS  MENINGITIS 

degree  of  temperature,  and  the  humidity.  It  dies 
readily  in  the  cerebrospinal  fluid  soon  after  its  re- 
moval from  the  body.  After  eighteen  hours,  as  a 
rule,  such  fluid  no  longer  yields  viable  organisms. 
Successful  cultures  from  cerebrospinal  fluid  demand 
the  use  of  considerable  quantities  (several  cubic  centi- 
metres) of  this  fluid.  In  autopsy  material  the  death 
of  the  meningococcus  is  even  more  rapid.  Distant 
transportation  of  such  material  is  therefore  to  be 
avoided  in  cultural  studies. 

When  first  isolated  from  the  body,  the  meningo- 
coccus will  not  grow  on  a  medium  that  does  not  con- 
tain animal  proteid.  Ascitic  agar  (ascitic  fluid  one 
part,  2  per  cent,  plain  or  glucose  agar  two  parts)  has 
been  found  by  the  greater  number  of  observers  to  be 
the  most  suitable  culture-medium  for  the  meningo- 
coccus. It  also  grows  well  on  pleuritic  agar,  sheep 
serum  agar,  blood  agar,  ascitic  bouillon,  and  Loeffler's 
serum.  At  first  it  requires  daily  transplantation  on 
these  media.  After  four  or  five  generations  trans- 
plantation once  a  week  is  sufficient.  Grown  for  some 
time  on  these  media  most  of  the  meningococcus  strains 
can  thereafter  live  on  plain  glucose  agar.  Sudden, 
unexpected  death  of  the  organism  is  not  a  rare  phe- 
nomenon. The  medium  should  be  neutral  or  slightly 
acid  (+0.8  to  phenolphthalein,  Elser  and  Hun- 
toon).    The  optimum  temperature  is  36.5°  to  37°  C. 


Fig.  5. — Colony  of  meningococcus.     Glucose  ascitic  agar. 


i;..    6      Plate  culture  of  meningococcus     Glucose  ascitic  agar. 


Fig.  7. — .Slant  culture  of  meningococcus.     Glucose  ascitic  agar. 


BACTERIOLOGY  21 

Growth  on  Ascitic  Agar  Plates  (Figs.  5  and  6). 
— At  the  end  of  twenty-four  hours'  growth  the  plate 
shows  small,  transparent,  glistening,  round  disks 
which  are  slightly  raised  and  have  a  moist  surface. 
The  diameter  of  the  colonies  is  about  one  to  three 
millimetres.  By  reflected  light  they  appear  gray 
or  grayish-white.  By  transmitted  light  some  colonies 
are  gray  and  uniformly  translucent,  others  have  a 
semi-opaque,  grayish-white  or  faintly  yellow  centre 
surrounded  by  a  transparent  peripheral  zone,  while 
others  show  several  zones  of  varying  opacity.  Seen 
through  a  low-power  lens,  the  colonies  appear  as 
faintly  yellow  disks,  having  well-defined  borders 
which  are  smooth  or  slightly  irregular. 

At  the  end  of  forty-eight  hours,  the  colonies  show 
slight  increase  in  size,  the  diameter  being  three  to 
four  millimetres.  The  surface  is  more  elevated,  and 
has  a  glistening  homogeneous  appearance.  The 
colonies  are  moderately  viscous,  not  adherent  to  the 
medium,  and  form  a  uniform  suspension  when  shaken 
in  salt  solution.  A  loopful  of  the  growth  is  grayish- 
white  in  color,  while  larger  masses  have  a  pinkish 
tint  when  added  to  a  colorless  medium. 

At  the  end  of  seventy-two  hours  crystalline  de- 
posits have  been  observed  by  Albrecht  and  Ghon, 
Bettencourt  and  Franca,  and  Elser  and  Huntoon. 
They  are,  however,  present  in  cultures  of  other  Gram- 


22         MENINGOCOCCUS  MENINGITIS 

negative  diplococci.  At  this  time  the  centre  becomes 
less  transparent  and  shows  a  distinctly  brownish  tint. 

Growth  on  Ascitic  Agar  Slants  (Fig.  7). — The 
most  abundant  growth  is  usually  seen  in  the  vicinity 
of  the  water  of  condensation,  where  the  moisture 
favors  the  growth  of  the  meningococcus.  Discrete 
colonies  of  varying  size  and  opacity  are  seen.  The 
water  of  condensation  presents  a  diffuse  turbidity, 
and  a  sediment  of  cocci  collects  at  the  bottom  of  the 
tube.  A  pellicle  may  appear  on  the  surface.  Traut- 
mann  and  Elser  and  Huntoon  have  seen  at  times 
a  more  or  less  distinct  greenish-yellow  discoloration 
of  the  medium  after  several  days'  growth.  This  pig- 
ment was  soluble  in  distilled  water  and  was  confined 
to  the  medium.  The  presence  of  glucose  favored  its 
occurrence.  Its  nature  was  not  determined.  In  very 
old  cultures  a  brownish  discoloration  of  the  medium 
is  frequently  observed. 

Growth  on  Blood  Agar. — The  meningococcus 
shows  a  very  viscid  growth  of  a  milky,  sometimes 
faintly  violet  or  greenish  tint.  It  is  more  opaque  and 
less  glistening  than  on  ascitic  agar. 

Growth  on  Ascitic  Broth. — When  not  disturbed 
a  delicate  pellicle  is  formed  on  the  surface  of  the 
broth.  The  medium  shows  a  diffuse  turbidity,  and  a 
sediment  collects  on  the  bottom  of  the  flask. 

Growth  on  potato  is  feeble  and  hardly  perceptible. 


BACTERIOLOGY  23 

Growth  in  milk  is  very  slight.  There  is  no 
coagulation. 

Conditions  Affecting  the  Viability  of  the  Menin- 
gococcus.— The  meningococcus  is  very  sensitive  to 
changes  in  humidity  and  temperature.  It  suffers 
marked  reduction  in  viability  when  exposed  to  direct 
sunlight.  This  lack  of  resistance,  as  we  shall  see 
later,  has  an  important  bearing  on  the  mode  of  dis- 
semination of  this  organism.  The  greater  resistance 
of  the  diplococcus  found  by  Jaeger,  which,  as  we 
stated  above,  he  identified  with  the  meningococcus, 
led  him  and  others  to  draw  far-reaching  but  errone- 
ous conclusions  regarding  the  mode  of  contagion  in 
this  form  of  meningitis.  All  those  who  have  dealt 
with  pure  cultures  of  the  meningococcus  have  reached 
practical  unanimity  as  regards  the  susceptibility  of 
this  organism  to  external  influences. 

Effect  of  Desiccation. — Cultures  in  which  proper 
precautions  are  not  taken  to  prevent  drying  die  within 
two  to  three  days.  Sealed  properly  the  organisms 
survive  more  than  fourteen  days.  Exposed  on  porous 
material,  such  as  filter-paper  or  linen,  they  lose  their 
vitality  in  six  hours  at  a  temperature  of  37°  C,  in 
twelve  hours  at  room  temperature.  Forty-eight  hour 
cultures  are  more  resistant  than  older  or  younger 
cultures. 

Effect  of  Eight. — In  diffuse  sunlight,  at  room 


24         MENINGOCOCCUS  MENINGITIS 

temperature,  the  meningococcus  survives  for  live  to 
seven  days  in  cultures.  After  eight  days  all  cultures 
are  killed.  The  effect  of  direct  sunlight  varies  some- 
what with  the  climate  and  season  of  the  year. 

Bettencourt  and  Franca,  in  Portugal,  found  that 
the  meningococcus  was  killed  after  two  hours'  ex- 
posure to  direct  sunlight.  In  Berlin,  during  June, 
v.  Lingelsheim  found  no  living  organisms  after  four 
to  five  hours'  exposure,  whereas  Kutscher,  in  the 
same  city,  during  March,  found  eight  to  twelve  hours' 
exposure  necessary.  Elser  and  Huntoon,  in  New 
York,  conducting  their  experiments  during  the  month 
of  August,  found  living  cultures  after  eight  and  nine 
hours'  exposure. 

Effect  of  Temperature. — The  meningococcus 
does  not  grow  below  25°  or  above  43°  C.  Some 
strains  fail  to  grow  above  41°.  Between  25°  and  31° 
C.  it  shows  but  feeble  growth.  In  the  ice-box  (8°  C.) 
it  may  survive  from  four  to  six  days.  At  10°  to  20° 
C.  it  is  killed  in  two  hours.  At  25°  to  26°  C.  in  a  dark 
room,  Elser  and  Huntoon  found  living  strains  on 
glucose  agar  at  the  end  of  three,  four,  or  five  weeks, 
v.  Lingelsheim  found  exposure  to  room  temperature 
fatal  to  the  meningococcus  in  five  days. 

Effect  of  Moist  Heat. — No  living  organisms  were 
found  by  v.  Lingelsheim  when  emulsions  were  ex- 
posed to  50°  C.  for  one  hour,  and  60°  C.  for  ten  min- 


BACTERIOLOGY 


25 


utes,  70°  C.  for  five  minutes,  80°  C.  for  two  minutes. 
Elser  and  Huntoon  found  that  a  temperature  of  45° 
C.  moist  heat  was  resisted  for  three  hours,  while  55° 
C.  was  resisted  by  some  strains  for  two  hours.  Betten- 
court  and  Franca  found  a  much  greater  suscepti- 
bility to  moist  heat. 

Effect  of  Disinfectant  Solutions. — This  table, 
based  on  Flugge's  experiments,  shows  the  effects  of 
various  disinfectants  on  the  meningococcus. 


3  per  cent,  hydrogen  peroxide  1 
1/10  per  cent,  to  1  per  cent 

corrosive   sublimate 
1  per  cent,  silver  nitrate 
1    per   cent,    to   2   per  cent, 

carbolic  acid 
1  per  cent,  lysol 
10  per  cent,  menthol 


kills  the  meningococcus  in  1 
minute. 


1  per  cent,  sulphuric  acid 

2  per  cent,  protargol 
70  per  cent,  alcohol 

1  per  cent,  lye 

1  per  cent,  hydrogen  peroxide  ) 
VL'  Pcr  cent,  protargol  J 


kills  the  meningococcus  in  2 
minutes. 

kills  the  meningococcus  in  7 
minutes. 

vills  the  meningococcus  in  9 
minutes. 


Dopter  and  Koch  found  that  when  essence  of 
eucalyptus,    bergamot,   origanum,   and   peppermint. 


26         MENINGOCOCCUS  MENINGITIS 

ether,  xylol,  and  formol  were  added  to  a  culture, 
growth  was  inhibited.  Koch  found  that  five  to  fif- 
teen drops  of  pyocyanase  added  to  a  bouillon  culture 
prevented  the  growth  of  the  meningococcus,  whereas 
one  cubic  centimetre  of  pyocyanase  added  to  an 
ascitic-agar  tube  retarded  growth  but  slightly.  A 
thick  emulsion  of  meningococci  in  pyocyanase  showed 
growth  when  added  to  bouillon  after  one-half  hour 
but  not  after  three  hours. 

Fermentation  of  Carbohydrates. — v.  Lingelsheim 
was  the  first  investigator  to  demonstrate  that  the 
meningococcus  ferments  only  dextrose  and  maltose. 
By  the  addition  of  litmus  to  a  culture-medium,  the 
formation  of  acid  is  readily  shown.  Buchanan,  Dunn 
and  Gordon,  and  Andrewes  claimed  fermentative 
action  on  galactose,  while  Arkwright  and  Andrewes 
found  that  not  only  was  galactose  fermented  but  also 
levulose.  Their  apparently  contradictory  results  have 
been  shown  by  Elser  and  Huntoon  to  be  due  to  the 
fact  that  these  sugars  when  heated  in  the  presence 
of  alkali  undergo  cleavage  into  dextrose.  To  obviate 
this  important  source  of  error,  they  advise  the  sepa- 
rate sterilization  of  the  sugar  dissolved  in  distilled 
water  in  old  Jena  glassware  which  has  been  steamed 
for  several  hours  so  as  to  reduce  to  a  minimum  the 
amount  of  alkali  given  off  by  the  glass.  Fermenta- 
tion by  the  meningococcus  of  dextrin  as  found  by 


BACTERIOLOGY  27 

Andrewes  is  probably  attributable  to  the  presence  of 
impurities.  Maquenne  has  shown  that  so-called 
chemically  pure  dextrin  contains  small  quantities  of 
maltose,  isomaltose,  or  dextrose.  According  to  v. 
Lingelsheim  and  Elser  and  Huntoon,  it  is  advisable 
to  use  solid  media  for  determination  of  fermentative 
action.  The  discordant  results  previously  obtained 
are  partly  attributed  by  these  observers  to  the  use  of 
liquid  media.  Xot  only  do  these  media  show  a  tardy 
reaction,  but  the  organism  may  fail  to  grow  in  them. 
Moreover,  a  microscopic  examination,  which  should 
always  be  made  to  determine  the  purity  of  the  growth, 
is  carried  out  more  readily  when  solid  media  are 
employed. 

Agglutination  Reaction, — In  1901  Albrecht  and 
Ghon  demonstrated  the  presence  of  specific  agglu- 
tinins in  the  sera  of  animals  repeatedly  injected  with 
cultures  of  the  meningococcus.  Jaeger  undertook 
a  systematic  investigation  of  this  property  of  the 
serum  in  rabbits.  Pie  apparently  proved  the  identity 
of  his  diplococcus  with  the  Weichselbaum  meningo- 
coccus by  showing  that  rabbits  injected  with  either 
organism  yielded  sera  which  agglutinated  both  of 
them.  These  results  Bettencourt  and  Franca  failed 
to  confirm  in  the  horse,  v.  Lingelsheim  found  that, 
while  meningococcus  immune  sera  (derived  from  the 
rabbit)  agglutinated  the  diplococcus  crassus  (Jaeger 


28         MENINGOCOCCUS  MENINGITIS 

diplococcus),  immune  sera  of  animals  injected  with 
diplococcus  crassus  failed  to  agglutinate  the  meningo- 
coccus. Jochmann  confirmed  the  observations  of 
Bettencourt  and  Franca  and  showed  that  there  was 
no  agglutination  relationship  between  the  two 
organisms. 

In  carrying  out  agglutination  tests  it  is  important 
to  have  controls  in  salt  solution  and  normal  sera. 
The  macroscopic  reaction  is  more  reliable  than  the 
microscopic.  The  technique  of  Elser  and  Huntoon 
is  as  follows :  Homogeneous  suspensions  are  made  in 
normal  salt  solution  containing  the  same  quantity  of 
moist  bacteria.  Equal  amounts  of  this  suspension 
are  thoroughly  shaken  in  test-tubes  containing  a 
graded  series  of  diluted  sera.  These  are  kept  in  the 
incubator  for  two  hours,  then  placed  in  the  ice-box 
for  twenty-two  hours.  Readings  are  made  at  one, 
two,  three,  four,  and  twenty-four  hour  intervals.  In 
most  cases  it  is  not  necessary  to  go  beyond  twenty- 
four  hours.  A  positive  agglutination  is  shown  by  the 
presence  of  clumped  cocci  at  the  bottom.  The  super- 
natant fluid  shows  a  slight  degree  of  uniform  turbid- 
ity. The  immune  sera  may  be  the  polyvalent  sera 
now  employed  for  treatment,  or  special  sera  derived 
from  animals  that  have  been  injected  intravenously 
with  increasing  doses  of  killed  meningococci. 

The  meningococcus  shows  variable  agglutinating 


BACTERIOLOGY  29 

activity,  the  same  strain  often  varying  markedly  from 
day  to  day.  Elser  and  Hnntoon  found  incomplete 
or  absent  agglutination  in  40  per  cent,  of  65  strains 
(1-100).  Killed  cultures  usually  give  more  uniform 
results.  Kutscher  advocates  testing  cultures  at  the 
temperature  of  55°  C.  In  this  manner  he  obtained 
positive  results  with  cultures  that  were  previously 
negative  at  37°  C.  Owing  to  the  presence  of  group 
agglutinins,  it  is  often  difficult  to  separate  by  this 
test  the  meningococcus  from  other  related  organisms. 
Xot  infrequently,  for  example,  the  gonococcus  yields 
positive  results  with  meningococcus  immune  sera  at 
dilutions  which  do  not  agglutinate  with  the  meningo- 
coccus. To  obviate  this  difficulty  absorption  tests  are 
employed. 

Absorption  Tests. — These  tests  depend  upon  the 
well-known  fact  that  specific  agglutinins  are  absorbed 
only  by  bacteria  which  belong  to  the  same  species  as 
those  employed  for  the  production  of  the  immune 
serum.  The  experiment  is  carried  out  by  adding  a 
suspension  of  the  meningococcus  to  an  immune  serum 
which  is  placed  in  the  incubator  for  2  hours  and  then 
centrifugalized.  Subsequent  addition  of  the  same  or 
another  strain  of  the  meningococcus  to  this  exhausted 
serum  shows  that  it  has  lost  a  large  part  of  its 
agglutinating  power.  This  loss  is  greater  with  the 
more  agglutinable  strains,  but  there  is  no  definite 


30         MENINGOCOCCUS  MENINGITIS 

relationship  between  absorptive  capacities  and 
agglutinability.  The  experiments  of  Dunham  seem 
to  prove  that  when  nitration  proceeds  slowly  a  con- 
siderable loss  of  agglutinability  results.  It  is  there- 
fore advisable  to  use  centrifugalization  in  doing 
absorption  tests.  These  tests  show  that  there  is  no 
group  relationship  between  the  meningococcus  and 
the  Jaeger  coccus. 

Precipitin  Reaction. — The  presence  of  meningo- 
coccus precipitins  was  shown  by  Bruckner  and  Chris- 
teanu  and  Dopter  and  Koch.  A  variable  quantity  of 
antimeningitis  serum  (one  to  two  drops)  is  added  to 
from  twenty  to  fifty  drops  of  an  aqueous  extract  or 
autolysate  of  the  meningococcus,  and  is  then  incubated 
for  twenty-four  hours.  A  positive  reaction  is  shown 
by  the  formation  of  a  precipitate. 

Complement  Fixation  Reaction. — This  reaction  is 
more  specific  than  either  the  agglutination  or  precipi- 
tin reaction,  as  the  fixation  of  complement  in  an  im- 
mune serum  occurs  only  with  the  homologous  antigen. 

Action  of  Bile  Salts. — Ficker  has  shown  that  a 
suspension  of  a  meningococcus  culture  becomes  clear 
on  addition  of  a  solution  of  bile  salts.  The  gono- 
coccus,  however,  yields  the  same  reaction.  The  test 
is  carried  out  as  follows : 

To  0.5  cubic  centimetre  of  an  emulsion  of  a 
twenty-four-hour  old  bouillon  culture    (one  loopful 


BACTERIOLOGY  31 

to  one  cubic  centimetre  of  physiological  salt  solution) 
add  0.1  cubic  centimetre  of  a  fresh  20  per  cent,  aque- 
ous solution  of  sodium  taurocholate.     The  mixture 
becomes  clear  immediately  or  after  one  hour's  incuba- 
tion at  37°  C. 

Peritoneal  Reaction. — This  was  first  demon- 
strated by  Dopter,  and  is  based  upon  the  Pfeiffer 
phenomenon.  One  cubic  centimetre  of  an  unheated 
antimeningitis  serum  is  injected  in  the  peritoneal 
cavity  of  a  young  guinea-pig  (2.50  grams) .  Exactly 
twenty-four  hours  later,  one-sixth  of  a  meningo- 
coccus culture  is  injected  intraperitoneally.  The 
peritoneal  exudate  within  twenty  to  thirty  minutes 
shows  few  or  no  free  meningococci.  Dopter  con- 
siders this  test  specific,  as  it  serves  to  differentiate 
the  meningococcus  not  only  from  the  pseudomenin- 
gococci,  but  also  from  the  parameningococcus. 

Intravenous  Reaction  {Epreuve  de  la  Veine). — 
Briot  and  Dopter  have  shown  that  when  a  young 
guinea-pig  is  injected  intravenously  with  a  mixture 
of  unheated  antimeningitis  serum  and  an  emulsion  of 
a  meningococcus  culture,  there  appear  within  a  few 
minutes  convulsions,  muscular  contractures,  dyspnoea, 
coma,  and  death.  This  reaction  occurs  with  the 
meningococcus  only,  and  is  due  either  to  a  peptotoxin 
or  the  bacteriolytic  action  of  the  serum.  The  occa- 
sionally  severe   symptoms   which   develop   in  horses 


32         MENINGOCOCCUS  MENINGITIS 

in  the  course  of  immunization  are  probably  of  the 
same  nature. 

Pathogenicity. — The  meningococcus  shows  feeble 
and  variable  pathogenic  action  on  the  usual  laboratory 
animals.  Subcutaneous  injections  are  usually  with- 
out effect.  Young  guinea-pigs  (weight  175  to  200 
grams)  and  white  mice  are  the  most  susceptible 
animals. 

Action  on  Guinea-Pigs. — Intraperitoneal  injec- 
tion in  guinea-pigs  produces  death  in  from  two  to 
five  days.  There  is  marked  reduction  in  temperature. 
The  animal  crouches  in  a  corner  with  hair  erect. 
The  abdominal  muscles  are  tense,  and  the  abdomen 
becomes  distended  with  gas.  If  death  occurs  in  less 
than  eighteen  hours,  the  exudate  is  scanty  and  poor  in 
leucocytes.  If  the  animal  dies  in  from  twenty-four 
to  thirty-six  hours,  more  characteristic  lesions  are 
seen.  There  is  an  abundant  free,  thick,  viscid,  yellow 
exudate,  especially  on  the  anterior  surface  of  the 
liver  and  rolled-up  omentum.  The  parietal  and 
visceral  peritoneum  shows  injection  of  its  vessels  and 
small  hemorrhages.  The  spleen  is  congested  and 
somewhat  increased  in  size.  There  is  gelatinous 
oedema  of  the  pancreas  and  pancreatic  tissue.  The 
adrenals  show  congestion  and  small  hemorrhagic  foci. 
There  is  an  increase  of  clear  fluid  in  the  pleural  cavity. 
Meningococci  are  found  in  variable  quantity  in  the 


BACTERIOLOGY  33 

peritoneal  exudate,  free  and  in  the  leucocytes.  They 
may  also  be  present  in  the  heart's  blood  and  in  the 
spleen.  If  the  animal  survives  for  five  to  six  days, 
peritoneal  exudate  is  absent  and  meningococci  are  not 
demonstrable.  Similar  lesions  are  found  in  white 
mice. 

Although  meningococci  have  been  found  in  the 
blood  and  abdominal  viscera,  indicating  a  general 
invasion,  it  is  probable  that  the  lesions  above  described 
are  due  to  an  intoxication  rather  than  infection,  since 
similar  lesions  have  been  produced  by  the  injection 
of  dead  meningococci  and  autolysate.  Elser  and 
Huntoon  were  able  to  recover  the  meningococcus 
from  the  blood  within  five  minutes  of  an  intraperi- 
toneal injection  of  a  culture,  at  a  time  when  multi- 
plication of  the  organism  was  out  of  the  question. 

Action  on  Rabbits. — Intravenous  injection  does 
not  produce  acute  symptoms.  The  animals  usually 
die  of  emaciation.  Hemorrhages  in  the  mucous  mem- 
brane of  the  gastro-intestinal  tract  have  been  found 
by  Elser  and  Huntoon.  These  lesions  favor  the 
passage  of  other  organisms  from  the  intestinal  tract, 
as  shown  by  feeding  experiments  with  typhoid  bacilli. 

Action  on  Dogs. — Suboccipital  injection  may  lead 
to  convulsions,  paralysis,  or  coma.  In  one  case  a 
transient  meningitis  was  produced. 


34         MENINGOCOCCUS  MENINGITIS 

Action  on  Goats. — Councilman,  Mallory  and 
Wright  succeeded  in  producing  a  meningitis. 

Action  on  Monkeys. — Successful  results  in  this 
animal  were  obtained  by  v.  Lingelsheim  and  Leuchs, 
Flexner,  and  Stuart  McDonald  by  intraspinal  injec- 
tion of  large  doses.  Before  death,  which  usually 
occurred  in  from  eighteen  to  twenty  hours,  the 
animals  exhibited  convulsions,  nystagmus,  dyspnoea, 
and  hyperesthesia.  At  autopsy  there  were  found  in- 
tense congestion  and  foci  of  extravasation  in  the  brain 
and  meninges.  A  thick  exudate  rich  in  leucocytes 
was  found  at  the  base  of  the  brain.  In  the  ventricles 
turbid  fluid  was  present.  Normal  or  degenerated 
meningococci  were  found  within  the  leucocytes. 

By  injecting  repeated  small  doses,  Flexner  suc- 
ceeded in  keeping  the  animals  alive  for  several  weeks. 
At  death  there  were  found  acute  and  chronic  lesions 
with  abundant  exudate  rich  in  leucocytes.  The  spinal 
dura  was  deeply  injected.  The  ventricle  and  central 
canal  of  the  cord  were  dilated,  and  hydrocephalus  was 
found  in  those  cases  where  the  foramen  of  Magendie 
was  occluded.  Although  these  lesions  are  very  similar 
to  those  found  in  the  natural  disease  in  man,  by  them- 
selves they  do  not  prove  the  selective  action  of  the 
meningococcus  for  the  meninges,  as  similar  inflamma- 
tory changes  in  the  meninges  of  animals  can  be  pro- 


BACTERIOLOGY  35 

duced  by  intraspinal  injections  of  a  number  of  pyo- 
genic bacteria. 

Difference  in  Strains. — Since  the  introduction  of 
specific  serotherapy,  the  biologic  differences  between 
various  strains  of  the  meningococcus  have  received 
extended  consideration.  We  have  previously  called 
attention  to  the  marked  variations  in  agglutinative 
capacity.  Differences  in  absorptive  capacity  and  in 
fixation  of  Complement  have  also  been  demonstrated. 
Other  differences  are  shown  in  the  culturability, 
survival  in  cultures,  and  power  to  ferment  carbo- 
hydrates. The  most  important  differences,  however, 
from  a  therapeutic  stand-point,  relate  to  variation  in 
pathogenic  power,  degree  of  digestibility  by  leu- 
cocytes, and  power  to  resist  solution  by  immune 
serum.  It  is  probable  that  some  cases  of  meningitis 
which  do  not  respond  satisfactorily  to  the  therapeutic 
action  of  the  serum  are  due  to  infection  by  strains  of 
the  organism  which  are  fast  to  the  antiserum 
employed. 

Gram-Negative  Cocci  in  the  Nasopharynx. — In 
the  course  of  the  numerous  investigations  on  the 
presence  of  the  meningococcus  in  the  nasopharynx, 
a  subject  of  supreme  theoretical  and  practical  im- 
portance, it  was  found  that  this  region  of  the  body 
constantly  harbors  a  number  of  Gram-negative  micro- 
organisms which  microscopically  closely  resemble  the 


36         MENINGOCOCCUS  MENINGITIS 

meningococcus.  Failure  to  take  this  fact  into  account 
renders  most  of  the  earlier  studies  on  this  phase  of 
the  subject  of  little  value.  As  a  result  of  the  admir- 
able work  of  v.  Lingelsheim  at  the  Beuthen  Station, 
we  are  now  in  possession  of  a  number  of  differential 
characteristics  which  enable  us  to  identify  and  classify 
most  of  these  organisms. 

According  to  Elser  and  Huntoon,  the  following 
Gram-negative  cocci  may  be  found  in  the  naso- 
pharynx of  man : 

1.  Meningococcus. 

(  Parameningococcus-Dopter. ) 

2.  Pseudomeningococcus,  separable  from  the  meningococcus 

only  by  absorption  tests. 

3.  Micrococcus  gonorrhoea  (Neisser). 

4.  Micrococcus  catarrhalis  (R.  Pfeiffer). 

5.  Micrococcus  pharyngis  siccus  (v.  Lingelsheim). 

6.  Chromogenic   Gram-negative   cocci : 

Group  I.  Ferments    dextrose,    maltose,    levulose,    and 

saccharose. 
Group  II.  Ferments  dextrose,  maltose,  and  levulose. 
Group  III.  Ferments  dextrose  and  maltose. 

Though  included  here  in  one  group,  there  is  no 
true  kinship  between  these  organisms  with  the  excep- 
tion of  the  meningococcus,  pseudomeningococcus,  and 
gonococcus,  which  possess  common  group  agglutinins. 

The  diplococcus  crassus  (or  Jaeger  coccus)  is  not 
included  in  this  list,  as  it  is  usually  Gram-positive. 


BACTERIOLOGY 


37 


Though  morphologically  hardly  distinguishable 
from  one  another,  they  possess  individual  cultural, 
fermentative,  and  agglutinating  characteristics  which 
are  sufficiently  well  marked  to  enable  us  to  separate 
them  into  distinct  species.  We  are  unable  to  enter 
here  into  a  description  of  the  character  of  the  cultures 
of  each  member  of  the  group.  The  reader  is  referred 
to  the  paper  by  Elser  and  Huntoon.  With  the  ex- 
ception of  the  pseudomeningococcus  and  gonococcus, 
the  cultural  appearance  does  not  resemble  that  of  the 
meningococcus.  The  pseudomeningococcus  can  be 
differentiated  from  the  meningococcus  only  by  the 
employment  of  absorption  tests.  The  gonococcus,  un- 
like the  meningococcus,  ferments  only  dextrose.  The 
fermentative  properties  of  the  members  of  this  group 
are  given  in  the  following  table,  from  Elser  and 
Huntoon : 


Number  of  strains. 


6 

o 

a 

o 

o 

00 

o 

S) 

o 

a 

o 

Q 

a 

Q 

i 

4) 

h3 

u 

Q 

OS 
02 

a 

a 

"a 

o 

■A 

o 

Q 

a 

OS 

0 

"5 
Q 

+ 

+ 

0 

0 

0 

0 

0 

0 

0 

+ 

+ 

0 

0 

0 

0 

0 

0 

0 

+ 

0 

0 

0 

0 

0 

0 

0 

0 

0 

0 

0 

0 

0 

0 

0 

0 

0 

+ 

+ 

+ 

+ 

0 

0 

0 

0 

0 

+ 

+ 

+ 

+ 

0 

0 

0 

0 

0 

+ 

+ 

+ 

0 

0 

0 

0 

0 

0 

+ 

+ 

0 

0 

0 

0 

0 

0 

0 

+ 

+ 

+ 

+ 

+ 

+ 

0 

0 

0 

+ 

+ 

+ 

+ 

+ 

+ 

0 

0 

0 

+ 

0 

0 

0 

0 

0 

0 

0 

0 

Meningococcus  200 

Pseudomeningococcus  6 

Gonococcus  15 

Micrococcus  catarrhalis  64  .  . . 
Micrococcus  pharyngis  siccus  2 
Chromogenic — 

Group  I     28 

Group  II    11 

Group  III    9 

Jaeger  micrococcus,  Krai  1. .  .  . 
Diplococcus  crassus,  Krai  1  .  . . 
Parameningococcus-!- 


38        MENINGOCOCCUS  MENINGITIS 

The  agglutination  reaction  is  another  valuable 
means  of  identifying  the  members  of  this  group.  Un- 
fortunately, its  value  is  considerably  reduced  by  the 
occurrence  of  many  inagglutinable  strains  amongst 
the  meningococci.  Some  investigators,  basing  their 
views  on  agglutination  reactions,  classify  the  menin- 
gococcus and  gonococcus  as  two  varieties  of  the  same 
species.  But  it  is  rather  strange  that  the  selective 
actions  on  the  tissues  of  the  body  are  so  different 
for  the  two  organisms, — one  for  the  meninges  and  the 
other  for  the  mucous  membrane  of  the  genito-urinary 
tract  and  joints.  Jundell  and  Zupnik  failed  to  pro- 
duce any  reaction  by  inoculation  of  meningococcus 
culture  on  the  urethra.  On  the  other  hand,  with  the 
exception  of  perhaps  one,  there  are  no  reliable  re- 
ports of  the  finding  of  gonococci  in  meningeal  exu- 
date. The  few  reports  extant  are  faulty  in  that 
culture,  fermentative,  and  absorption  tests  were  not 
made. 

Parameningococcus. — In  1909  Dopter  found  in 
the  nasopharynx  an  organism  which  closely  resembled 
the  meningococcus,  but  which  showed  slight  or  no 
agglutination  with  antimeningitis  serum.  Subsequent 
studies  by  this  observer  demonstrated  the  fact  that  it 
possessed  specific  agglutinins  and  precipitins,  and 
that  with  an  antimeningococcus  serum  it  failed  to  re- 
spond to  his  peritoneal  and  intravenous  tests.  Carnot 


BACTERIOLOGY  39 

and  Marie  found  this  organism  in  the  blood  of  a  fatal 
case  of  malignant  purpura,  and  Menetrier  and  Brodin 
first  described  a  meningitis  due  to  the  parameningo- 
coccus. Since  then  more  than  a  dozen  such  cases  have 
been  recorded  by  various  French  observers.  In  one 
case  of  Widal  and  Weissenbach  no  effect  was  seen 
from  the  use  of  antimeningococcus  serum  (Dopter). 
The  subsequent  application  of  an  antiparameningo- 
coccus  serum  prepared  by  Dopter  resulted  in  a  cure. 

Bibliography 
Marchiafava  and  Celli:    Gazz.  dcgli  Ospedali,  1884,  v,  59. 
Leichtenstem :     Deut.  med.  Wochcnschr.,  1885,  xi,  391. 
Weichselbaum :    Fortschrit.  d.  Med.,  1887,  v,  573. 
Goldschmidt:    Centr.  f.  Bakt.  u.  Parasit.,  1887,  ii,  649. 
Bonome:    Ziegler's  Beitriig,  1890,  viii,  377. 
Jaeger:    Zeit.  f.  Hyg.  u.  Infect,  1895,  xix,  351. 
Heubner:  Jahrb.  f.  Kinderhk.,  1896,  xlviii. 

Deutsche  med.  Wochenschr.,  1896,  xxii,  423. 
Deutsche  med.  Wochenschr.,  1897,  xxiii,  Vereins- 
beilag,  109. 
Councilman,    Mallory    and   Wright:      Report    of   the    State 

Board  of  Health  of  Mass.,  Boston,  1898. 
Netter:  Twentieth  Century  Practice,  New  York,  1899,  xvi, 

143. 
Weichselbaum:      Centr.    f.    Bakt.   u.    Parasit.,    1903,   xxxiii, 

1  Abt.  Orig.,  510. 
Kolle  and  Wassermann :    Handbuch,  1903,  iii,  256. 


40         MENINGOCOCCUS  MENINGITIS 

Albrecht  and  Ghon :    Centr.  f .  Bakt.  u.  Parasit.,  1903,  xxxiii, 

1  Abt.  Orig.,  496. 
Celler:    Mt.  Sinai  Hosp.  Reports,  1903,  iii,  543. 
Libman:    Mt.  Sinai  Hosp.  Reports,  1903,  iii,  546. 
Bettencourt   and  Franca:     Zeit.   f.   Hyg.   u.   Infect.,   1904, 

xlvi,  463. 
Koplik:    Med.  News,  1904,  lxxxiv,  1065. 
Dunham:     Jour.  Inf.  Diseases,  1906,  Suppl.  2,  1,0. 
Elser:    Jour.  Med.  Research,  1905-1906,  xiv,  89. 
Kolle  and  Wassermann:    Klin.  Jahrbuch,  1906,  xv,  507. 
v.  Lingelsheim :    Klin.  Jahrbuch,  1906,  xv,  373. 
Bruckner  and  Christeanu :    Soc.  de  Biol.,  1906,  lx,  846,  907, 

988,  1070. 
v.  Lingelsheim  and  Leuchs :    Klin.  Jahrbuch,  1906,  xv,  489. 
Kutscher:       Kolle     and     Wassermann     Handbuch,     1907, 

Erganzbd.  i,  481. 
Flexner:    Jour.  Exp.  Med.,  1907,  ix,  105. 
Jour.  Exp.  Med.,  1907,  ix,  142. 
Ditthorn  and  Gildmeister:    Klin.  Jahrbuch,  1907,  xvii,  95. 
McDonald:    Jour.  Path,  and  Bact.,  1908,  xii,  442. 
McKenzie  and  Martin :    Jour.  Path,  and  Bact.,  1908,  xii,  539. 
Wilson :    Lancet,  1908,  ii,  477. 
Symmers:    Brit.  Med.  Jour.,  1908,  ii,  1334. 
Dopter  and  Koch :    Compt.  rend.  Soc.  de  Biol.,  1908,  lxv,  215. 
Compt.  rend.  Soc.  de  Biol.,  1908,  lxv,  285. 
Krumbein  and  Schatiloff:    Deutsche  med.  Wochenschr.,  1908, 

xxiv,  1002. 
Koch:    Etudes  Bacteriologiques  aus  le  Meningocogne,  These 

de  Paris,  1908-1909. 
Ditthorn  and  Woerner:    Hyg.  Rundschau,  1909,  xiv,  1. 


BACTERIOLOGY  41 

Elser  and  Huntoon:   Jour.  Med.  Research,  1909,  xx,  377. 

Ficker:    Arch.  f.  Hyg.,  1909,  lxviii,  1. 

Dopter:    Corapt.  rend.  Soc.  de  Biol.,  1909,  Ixvi,  772,  1055. 

1909,  lxvii,  74. 

1910,  lxix,  600. 
Briot  and  Dopter:     Compt.  rend.  Soc.  de  Biol.,  1910,  lxix, 

10, 126. 
Netter  and  Debre:  La  Meningite  Cerebrospinale,  Paris,  1911. 


CHAPTER  III 

Epidemiology 

The  epidemiology  of  meningococcus  meningitis 
presents  features  which  are  not  often  seen  in  other 
epidemic  diseases.  At  times  they  have  been  so  strange 
and  puzzling  and  so  different  from  the  characteristics 
usually  associated  with  a  contagious  disease  that  the 
contagiousness  has  been  questioned  by  not  a  few 
observers.  In  periods  of  wide-spread  epidemics  it  has 
usually  been  impossible  to  trace  the  progress  of  the 
contagion  from  one  locality  to  another.  As  a  rule, 
there  is  no  regular  progression  or  extension  of  the 
disease.  It  moves  by  leaps  and  bounds,  and  seems 
to  strike  at  haphazard.  Simultaneously  affected 
localities  are  often  separated  by  those  that  almost 
wholly  escape  the  infection.  The  evolution  of  an 
epidemic  is  usually  slow  and  gradual,  and  there  is 
no  regular  cycle  as  observed  in  epidemics  of  other 
disease.  The  cases  are  scattered  and  seem  to  be 
grouped  around  several  small  foci  instead  of  a  single 
focus.  Physicians  and  hospital  attendants  rarely 
contract  the  disease,  while  a  multiplicity  of  cases  in  a 
family  or  dwelling  is  rather  unusual  and  in  certain 
epidemics  has  been  entirely  absent.  Moreover,  as 
compared  with  other  epidemics,  but  a  small  propor- 

42 


EPIDEMIOLOGY  43 

tion  of  the  population  contracts  the  disease.  This 
feature  is  especially  noticeable  in  large  cities,  the 
morbidity  rate  from  epidemic  meningitis  in  the  four 
large  epidemics  that  occurred  in  New  York  City 
having  been  as  follows: 

1872    8.07  per  10,000 

1881  3.70  per  10,000 

1893        2.67  per  10,000 

1904-1905 6.30  per  10,000 

In  smaller  communities  the  relative  number  of  cases 
may  be  much  higher,  as  in 

Lippisch  (near  Danzig)    1250  per  10,000 

Aigue-Mortes,  1841    533  per  10,000 

Strassburg,  1841 30  per  10,000 

As  a  rule,  the  disease  in  large  cities  does  not 
attack  more  than  1  to  2  per  10,000  of  the  population. 
This  is  a  much  smaller  morbidity  rate  than  that  of 
measles,  scarlet  fever,  diphtheria,  pneumonia,  or 
typhoid  during  periods  free  from  epidemics  of  these 

diseases. 

Contagiousness.— Despite  the  epidemiologic  facts 
above  stated,  there  can  be  little  doubt  regarding  the 
contagiousness,  feeble  though  it  is,  of  this  form  of 
meningitis.  Those  clinicians  who  have  denied  it  have 
based  their  conclusions  on  personal  experience  during 
a    limited    number    of    epidemics    in    which    certain 


44         MENINGOCOCCUS  MENINGITIS 

features  which  we  are  accustomed  to  associate  with 
a  contagious  disease  were  absent.  It  is  not  strange 
that  Vieusseux,  the  first  to  recognize  the  disease  as  a 
clinical  entity,  held  this  opinion.  In  the  epidemic 
at  Geneva  during  the  latter  part  of  the  year  1805, 
the  disease,  which  began  in  the  crowded  quarters  of 
the  city,  did  not  apparently  extend  from  case  to  case. 
The  attendants  on  the  sick  and  their  neighbors 
uniformly  escaped  infection.  In  those  dwellings  in 
which  there  was  more  than  one  case,  the  patients  did 
not  acquire  the  disease  from  one  another,  as  it  ap- 
peared not  successively  but  simultaneously.  Berg,  in 
the  New  York  epidemic  of  1893,  was  unable  to  find 
amongst  his  patients  a  single  instance  in  which  more 
than  one  member  of  a  family  contracted  the  disease. 
In  the  epidemic  of  1904-1905,  however,  he  encoun- 
tered a  number  of  such  instances. 

Bearing  in  mind  the  feeble  infective  power  of  the 
meningococcus  for  the  meninges,  it  becomes  evident 
that  a  small  number  of  undoubted  instances  of  trace- 
able contagion  is  infinitely  more  convincing  than 
much  negative  evidence.  The  literature  teems  with 
many  indubitable  instances  of  direct  contagion. 
Netter  and  Debre  quote  Sewall's  observation  during 
the  New  York  epidemic  of  1872  in  which  six  members 
of  the  Brown  family  successively  contracted  the 
disease  at  intervals  of  from  one  to  thirty-four  days. 


EPIDEMIOLOGY  45 

Peterson,  as  a  result  of  a  very  thorough  investigation 
of  an  epidemic  in  Berlin,  succeeded  in  tracing  direct 
contagion  between  thirty-four  cases.  Cholard  reports 
the  occurrence  of  three  cases  of  meningitis  in  the 
family  of  a  wood-cutter  living  in  a  completely  isolated 
cabin  in  a  forest  of  Braubourg.  The  outbreak 
occurred  a  few  days  after  the  return  of  the  head  of 
the  family  from  the  military  manoeuvres  at  Evreaux, 
where  an  epidemic  was  prevalent  at  the  time.  Accord- 
ing to  Bolduan  and  Goodwin,  there  were,  among 
1500  cases  in  the  New  York  epidemic  of  1904-1905, 
88  instances  of  more  than  one  case  in  a  house,  thus — 

39  instances  in  which  there  were  2  cases  in  a  house 

15  instances  in  which  there  were  3  cases  in  a  house 

2  instances  in  which  there  were  4  cases  in  a  house 

1  instance    in  which  there  were  5  cases  in  a  house 

1  instance    in  which  there  were  8  cases  in  a  house 

In  34  instances  the  intervals  between  the  appear- 
ance of  the  cases  were  as  follows : 

In  9  instances  the  interval  was  4  days  or  less 
In  5  instances  the  interval  was  4-7  days 
In  5  instances  the  interval  was  1-2  weeks 
In  4  instances  the  interval  was  2-3  weeks 
In  3  instances  the  interval  was  3-4  weeks 
In  2  instances  the  interval  was  4—5  weeks 
In  3  instances  the  interval  was  5-6  weeks 
In  2  instances  the  interval  was  7-8  weeks 
In  1  instance    the  interval  was  3  months 


46         MENINGOCOCCUS  MENINGITIS 

In  three  instances  the  disease  seems  to  have  been 
communicated  to  or  by  the  family  of  the  janitors. 
School  contagion  seemed  probable  in  two  instances. 

Contrasted  with  the  many  records  of  immunity 
from  contagion  in  general  hospitals,  a  fact  which 
(as  we  shall  see  later)  is  attributable  to  the  general 
absence  of  meningococcus  carriers  in  these  institu- 
tions, is  the  report  by  Leichtenstern  of  a  small  epi- 
demic in  the  Cologne  Hospital.  Three  nurses  and  a 
sister  in  attendance  on  cases  of  meningitis  in  the  wards 
contracted  the  disease.  Three  of  them  had  not  left 
the  hospital  for  some  time  and  could  not  have  acquired 
the  disease  from  the  outside.  Montanari,  likewise, 
reports  the  infection  of  a  nurse  and  her  two  daughters 
in  a  hospital  at  Foggia.  In  the  New  York  Hospital, 
Elser  and  Huntoon  found  three  instances  of  infec- 
tion of  nurses  in  attendance  on  adult  cases  of  menin- 
gitis. Cases  of  school  contagion,  though  rare,  are 
reported  by  Bolduan  and  Goodwin  and  Netter  and 
Debre.  The  latter  observed  10  cases,  6  of  which 
attended  a  common  school.  Among  231  pupils  of  this 
school  there  were  found  40  meningococcus  carriers, — 
i.e.,  21.21  per  cent. 

A  number  of  instances  of  the  spread  of  an  epi- 
demic from  one  locality  to  another  along  the  routes 
of  travel  are  recorded  in  the  literature.  According 
to  Netter  and  Debre,  the  progress  of  the  French 


EPIDEMIOLOGY  47 

epidemic  of  1837-1850  from  the  southwest  to  the 
northeast  is  traceable  to  the  movements  of  the  18th 
Regiment  of  the  French  army.  The  same  authors 
attribute  the  Algerian  epidemic  of  1840  to  the  pres- 
ence of  a  French  garrison.  The  epidemic  in  Italy  of 
the  same  period,  which  began  in  Ancone,  is  also 
attributable  to  intercourse  with  the  French  army. 

In  the  literature,  instances  are  recorded  of  the 
spread  of  an  epidemic  from  an  infected  garrison  to 
the  civil  population.  In  Strassburg,  Schlestadt,  and 
Metz  the  first  cases  in  the  civil  community  occurred 
in  the  streets  adjoining  the  barracks.  In  Foggia  the 
epidemic  appeared  after  the  arrival  of  a  recruit  from 
Viesto,  where  the  disease  existed  the  previous  year. 

Geographic  Distribution. — Meningococcus  menin- 
gitis shows  the  greatest  prevalence  in  the  north 
temperate  zone.  Epidemics,  however,  have  been  seen 
as  far  north  as  Iceland,  and  as  far  south  as  Java  and 
Soudan.  The  historical  sketch  shows  that  no  part  of 
the  civilized  world  has  escaped  its  visitation.  North- 
eastern United  States,  France,  and  Germany  have 
shown  special  liability  to  epidemic  outbreaks. 

Seasonal  Incidence. — Epidemics  of  meningitis 
usually  begin  in  the  winter  and  reach  their  maximum 
intensity  in  the  spring  months.  Relatively  few  epi- 
demics have  been  seen  in  the  summer  and  autumn. 
Of  85  American  epidemics  recorded  by  Hirsch,  37 


48 


MENINGOCOCCUS  MENINGITIS 


occurred  in  the  winter,  18  in  the  winter  and  spring, 
and  23  in  the  spring.  According  to  Aitken,  311  of 
417  epidemics  in  Sweden  occurred  in  the  winter.  In 
the  Prussian  epidemic  during  1905  to  1908,  the  dis- 
tribution of  the  cases  was  as  follows: 


December,  January,  February. . 

March,  April,  May 

June,  July,  August 

September,  October,  November 


1905. 


531 

2545 

535 

151 


1906. 


580 

1031 

258 

160 


1907. 


466 

1254 

577 

286 


1908. 


353 
609 
199 
125 


Total 
per 
cent. 


18.2 

61.0 

14.8 

6.0 


From  these  figures  it  can  be  seen  that  approximately 
80  per  cent,  of  the  cases  occurred  in  the  winter  and 
spring  months.  In  New  York  in  1904  the  epidemic 
began  in  March  and  reached  its  height  in  May;  the 
next  year  it  began  in  February  and  attained  its  maxi- 
mum in  March.  While  many  of  the  reported  epi- 
demics have  occurred  in  unusually  severe  winters,  not 
a  few  have  been  seen  in  unusually  mild  weather,  as  at 
Metz  in  1839-1840,  Italy  in  1839-1840,  1840-1841, 
Indiana  in  1862-1863,  Kentucky  in  1866.  The  epi- 
demic at  Smyrna  in  1868-1870  occurred  during  an 
excessively  hot  spring.  No  satisfactory  explanation 
for  the  seasonal  prevalence  has  as  yet  been  offered. 
Perhaps  it  is  due  to  the  frequency  of  "  colds  "  and 
respiratory  affections  at  this  time  of  the  year. 


EPIDEMIOLOGY  49 

Age  Incidence. — Epidemic  meningitis,  though 
seen  at  all  ages,  is  pre-eminently  an  affection  of  child- 
hood and  adolescence.  In  the  Prussian  epidemic  of 
1905-1907,  6623  of  8198  patients,  i.e.,  80.12  per  cent., 
were  below  sixteen  years  of  age.  In  the  Swedish  epi- 
demic of  1855-1860  there  were,  according  to  Hirsch, 
889  cases  below  fifteen  years  of  age,  328  between  six- 
teen and  forty  years,  and  only  50  cases  over  fifty 
years,  in  a  total  of  1267  fatal  cases.  Goeppert  in 
Silesia  saw  14.46  per  cent,  of  his  cases  in  the  first  two 
years  of  life.  On  the  other  hand,  in  a  large  number  of 
military  epidemics  children  have  escaped  entirely.  In 
some  of  the  non-military  outbreaks,  as  at  Mont- 
gomery, Alabama,  adult  victims  were  in  the  great 
majority. 

The  pronounced  susceptibility  of  infants  and 
children  to  meningococcic  infection  has  received  a 
number  of  explanations,  no  one  of  which  is  quite 
satisfactory.  Cuneo  and  Veau  claim  to  have  found, 
during  the  periods  of  infancy  and  childhood,  direct 
anatomical  communication  in  the  sphenoid  bone  be- 
tween the  lymphatics  of  the  nasopharynx  and  the 
meninges.  These  lymphatic  canalicules  become  ob- 
literated in  adult  life.  To  attribute  the  greater  inci- 
dence of  meningitis  in  childhood  to  this  alleged  ana- 
tomical condition  at  the  base  of  the  cranium  would 
necessitate  the  adoption  of  the  view  that  infection  of 

4 


50         MENINGOCOCCUS  MENINGITIS 

the  meninges  takes  place  by  direct  extension  from  the 
nasopharynx.  As  we  shall  see  in  a  subsequent 
chapter,  there  are  many  weighty  reasons  that  speak 
against  this  assumption.  WestenhoefFer  attributes 
the  predisposition  to  meningeal  infection  in  childhood 
to  the  hyperplastic  condition  of  the  adenoid  tissue  at 
this  period  of  life.  His  pathologic  studies  showing 
the  more  frequent  occurrence  of  the  "  lymphatic 
state  "  in  those  who  contract  the  disease,  as  contrasted 
with  those  who  escape  infection,  are  not  borne  out  by 
the  investigations  of  E.  Meyer  and  others.  More- 
over, the  special  susceptibility  of  childhood  is  not  an 
exclusive  feature  of  meningococcus  meningitis.  A 
number  of  infectious  processes  exhibit  the  same  pecu- 
liarity. The  frank  admission  must  be  made  that  the 
special  factors  involved  in  this  phase  of  infection  and 
immunity  are  not  known. 

Sex  Incidence. — The  influence  of  sex  is  not  a 
factor  of  importance.  Epidemics  in  which  the  disease 
attacked  a  greater  number  of  individuals  of  one  or 
the  other  sex  are  reported  in  the  literature.  As  a  rule, 
however,  the  distribution  of  the  disease  is  about  equal 
in  the  two  sexes. 

Race  Incidence. — The  relative  incidence  of  the 
disease  among  the  Caucasian  and  African  races  in 
regions  inhabited  by  both  has  varied  greatly  in  differ- 
ent   epidemics.      In    the    early    epidemics    in    New 


EPIDEMIOLOGY  51 

Orleans  and  Memphis,  negroes  were  chiefly  affected; 
while,  in  the  recent  epidemic  in  Texas,  three  times  as 
many  whites  as  negroes  contracted  the  disease. 

Influence  of  Hygienic  Conditions. — Epidemics  of 
meningitis  are  seen  most  often  in  the  crowded  districts 
of  a  city  or  province.  In  New  York  and  other  large 
cities  the  densely  populated  quarters  inhabited  largely 
by  immigrants  have  repeatedly  borne  the  brunt  of  an 
epidemic.  The  recent  severe  outbreaks  in  Silesia  and 
Westphalia  claimed  most  of  their  victims  among  the 
families  of  the  miners  working  in  the  dark  and  damp 
coal  galleries.  Jehle  has  shown  that  the  infection 
could  be  traced  to  the  men  working  in  the  mines,  and 
not  to  the  intercourse  existing  between  their  families. 
This  he  attributes  to  the  great  frequency  of  catarrhal 
conditions  of  the  pharynx  existing  among  the  miners 
and  to  their  habit  of  indiscriminate  expectoration. 

It  is  probable  that  the  frequency  of  epidemics 
among  soldiers  is  due  to  overcrowding  in  the  barracks. 
It  has  been  repeatedly  observed  that  newly  arrived  re- 
cruits fell  victims  to  the  disease.  This  predisposition 
has  been  attributed  to  fatigue  as  a  result  of  the 
strenuous  drills  to  which  the  recruits  had  not  pre- 
viously been  accustomed.  However,  if  this  were  the 
case  we  should  expect  to  find  an  increase  of  the 
disease  during  campaigns.  Meningococcus  meningi- 
tis, however,  is  not  a  war  pestilence. 


5%        MENINGOCOCCUS  MENINGITIS 

The  character  and  condition  of  the  soil,  a  frequent 
topic  of  controversial  discussion  in  other  epidemic 
diseases,  elevation,  and  degree  of  moisture  play  a  role 
of  subordinate  importance.  Epidemics  of  meningitis 
have  been  equally  as  frequent  in  sandy  and  alluvial 
soil,  and  in  hilly  and  level  regions. 

The  Condition  of  the  Patient. — A  great  number 
of  victims  have  been  in  perfect  health  at  the  time  the 
disease  was  contracted.  Traumatism  to  the  base  of 
the  cranium  is  mentioned  occasionally  in  the  casuistic 
literature.  In  the  vast  majority  of  the  cases  this 
etiologic  factor  has  not  been  present.  In  many  epi- 
demics of  meningitis  a  simultaneous  increase  in  a 
number  of  infectious  diseases,  such  as  scarlet  fever, 
influenza  and  pneumonia,  has  been  noted. 

Sporadic  Cases. — At  the  present  time  it  is  hardly 
necessary  to  insist  on  the  identity  of  the  sporadic  and 
epidemic  forms  of  meningococcus  meningitis.  A  con- 
siderable number  of  isolated  cases  occur  annually  in 
all  the  larger  cities.  The  approach  of  an  epidemic 
is  frequently  heralded  by  an  increase  in  the  number 
of  cases.  A  similar  increase  in  the  sporadic  incidence 
of  meningitis  is  seen  in  the  wake  of  an  epidemic. 
This  is  well  shown  in  the  statistics  of  New  York  City. 

1890    136  cases 

1891    189  cases 

1892    230  cases 


EPIDEMIOLOGY  53 

1893  469  cases     (epidemic) 

1894  214  cases 

1895  204  cases 

1896  173  cases 

1897  221  cases 

1898  310  cases 

1899  372  cases 

1900  201  cases 

1901  201  cases 

1902  190  cases 

1903  195  cases 

1904    1083  cases     (epidemic) 

1905    2755  cases 

1906    1032  cases 

1907  828  cases 

1908  380  cases 

1909  346  cases 

1910  342  cases 

1911  266  cases 

1912  250  cases 

Bibliography 

Leichtenstern :    Deutsche  med.  Wochenschr.,  1885,  xi,  391. 
Hirsch:     Historisch  Geographische  Path.,  Stuttgart,  1886, 

2  Aufl.  111. 
Berg:    Archives  of  Pediatrics,  1894,  xi,  352. 
Montanari:    Gior.  della.  Reale.  Soc.  Ital.  d'igien,  1894,  xvi, 

405. 
Petersen:   Deut.  med.  Wochenschr.,  1896,  xxii,  579. 
Andre:    Contrib.   a  l'etude  des   lymphatiques  der  nez,  etc., 

These  de  Paris,  1904-1905. 
Bolduan  and  Goodwin:    Med.  News,  1905,  lxxxvii,  1222. 


54         MENINGOCOCCUS  MENINGITIS 

Westenhoeffer :    Klin.  Jahrbuch,  1906,  xv. 

Berl.  klin.  Wochenschr.,  1906,  xliii,  1267. 
Goeppert:    Klin.  Jahrbuch,  1906,  xv. 
Meyer:     Klin.  Jahrbuch,  1906,  xv. 
Jehle:    Wiener  klin.  Wochenschr.,  1906,  xix,  753. 
Westenhoeffer:     Berl.  klin.  Wochenschr.,  1907,  xliv,  1213. 
Goeppert:   Ergeb.  d.  Inner  Med.  u.  Kinderhk.,  1909,  iv,  165. 
Elser  and  Huntoon :    Jour.  Med.  Research,  1909,  xx,  377. 
Netter  and  Deb  re :    La  Meningite  cerebrospinale,  Paris,  1911. 


CHAPTER  IV 

Mode  of  Dissemination 

Having  established  the  contagious  nature  of 
meningococcus  meningitis,  the  problem  of  the  mode 
of  its  dissemination  remains  to  be  discussed.  The 
earlier  observers,  even  those  who  suspected  the  in- 
fectious nature  of  the  disease,  were  at  a  loss  how  to 
explain  the  mode  in  which  the  disease  was  trans- 
mitted. Although  catarrhal  inflammation  of  the 
nasopharynx  is  a  condition  frequently  present  in 
meningococcus  meningitis,  it  rarely  gives  evidence 
of  its  existence  by  pronounced  subjective  or  objec- 
tive symptoms.  It  is  the  more  likely  to  be  over- 
looked as  the  patients  are  often  apathetic  and 
stuporous.  The  coryza  sometimes  present  in  menin- 
gitis, though  much  less  frequent  than  the  inflamma- 
tion of  the  nasopharynx,  naturally  first  engaged 
the  attention  of  the  earlier  observers,  and  nasal 
cultures  were  first  employed  in  the  search  for  the 
meningococcus.  A  great  advance  in  our  knowledge 
of  this  phase  of  the  problem  was  made  when  the 
meningococcus  was  demonstrated  in  the  throat  of 
meningitis  patients.  Kiefer  and  Councilman, 
Mallory  and  Wright  found  meningococci  in  the 
throat  of  patients,  but  it  remained  for  Albrecht  and 

55 


56 


MENINGOCOCCUS  MENINGITIS 


Ghon,  in  1901,  to  establish  the  frequency  of  this  phe- 
nomenon. Their  observations  were  confirmed  by 
Lord,  Weichselbaum,  and  all  observers  of  the  recent 
epidemics  in  Germany,  America,  England,  and 
France.  The  earlier  results  were  frequently  nega- 
tive. When  it  was  realized  what  a  delicate  organism 
the  meningococcus  is,  cultures  were  made  under  better 
conditions,  and  positive  results  became  more  numer- 
ous. At  first  v.  Lingelsheim  found  the  meningo- 
coccus in  only  182  out  of  787  cases,  or  23.12  per  cent.; 
when  the  cultures  were  incubated  at  once,  46  out  of 
49  cases,  or  93.8  per  cent,  yielded  positive  results. 
That  the  meningococcus  disappears  rapidly  from  the 
nasopharynx  of  meningitis  patients  is  well  shown  by 
the  statistics  of  this  observer,  which  are  as  follows : 


Day  of  disease. 

Number  of 
specimens 
examined. 

Number  of 
specimens 
positive. 

Percentage 

of  positive 

results. 

First  to  fifth  day 

156 
57 
62 

115 

104 
14 

7 
5 

66.6 

Sixth  to  tenth  day 

24.56 

Eleventh  to  thirtieth  day 

Twenty-first  day  or  later 

11.29 
4.39 

The  figures  of  Goodwin  and  v.  Sholly  and  Netter 
and  Debre  exhibit  the  same  tendency. 


Goodwin  and  V.  Sholly. 

Netter  and 
Debre. 

First  week 

12  out  of  22  =  54°  5 
5  out  of  15=33.3 

1  out  of  16  =  6.25 

p.  ct. 

78.55 

Second  week 

60.0 

Third  week 

50.0 

Fourth  week 

25.0 

After  1  month 

15.35 

MODE  OF  DISSEMINATION  57 

By  itself  the  presence  of  the  meningococcus  in  the 
nasopharynx  of  patients  fails  to  explain  the  spread 
of  the  disease,  which,  as  we  have  seen,  rarely  occurs 
directly  from  patient  to  patient.  The  natural  history 
of  the  meningococcus  makes  it  improbable  that  the 
disease  is  transmissible  through  the  agency  of  the 
atmosphere  or  lifeless  objects.  Its  extreme  suscepti- 
bility to  drying  renders  its  life  outside  the  body  a 
precarious  one.  The  problem  of  the  mode  of  trans- 
mission of  the  disease  received  its  final  solution  when 
it  was  discovered  that  the  nasopharynx  of  persons 
coming  in  intimate  contact  with  patients  harbored  the 
meningococcus.  This  fact  was  first  discovered  by 
Albrecht  and  Ghon  in  1901.  They  found  the  menin- 
gococcus in  the  throat  of  a  man  whose  child  died  of 
meningitis.  Since  this  epoch-making  discovery  an 
extensive  literature  has  accumulated  tending  to  show 
the  existence  of  a  large  number  of  healthy  germ 
carriers.  It  has  been  estimated  by  Fliigge  that  the 
number  of  carriers  is  ten  to  twenty  times  as  great  as 
the  number  of  meningitis  cases  developing  during  the 
same  period.  The  same  observer  finds  that  seventy 
per  cent,  of  the  individuals  living  in  close  proximity 
to  a  meningitis  patient  become  carriers.  The  results 
of  the  most  important  investigations  on  this  phase  of 
the  subject  are  shown  in  the  following  table,  taken 
from  Frost: 


58 


MENINGOCOCCUS  MENINGITIS 


Demonstration  of  the  Meningococcus  in  the  Nasopharynx  of  Apparently 
Healthy  Persons. 


Locality. 


Condition. 


Dieudonne'  (1906),  during 
small  outbreak  in  garri- 
son at  Munich,  examined 
(Centralblatt  f.  Bakt., 
1906,  p.  418): 


Osterman  (1905-06),  during 
an  epidemic  in  vicinity 
of  Breslay,  examined 
(Deutsch.  med.  Wochen- 
schr.,  1906,  1,  p.  414): 


Bochalli,  in  garrison  at  Beu- 
then,  Prussia,  in  which 
there  had  been  a  case 
recently,  examined  (Zeit- 
schr.  f.  Hyg.  u.  Infek- 
tionskrank.,  Bd.  lxi,  pp. 
454-464) : 


Von  Lingelsheim,  in  vicin- 
ity of  Beuthen,  Prussia, 
during  an  epidemic,  ex- 
amined (Zeitschr.  f.  Hyg. 
u.  Infektionskrank.,  1908, 
Bd.  59,  pp.  457-483): 


Bruns  and  Hohn,  in  valley 
of  the  Ruhr,  Prussia,  dur- 
ing severe  epidemic  in 
1907,  examined  (Klin. 
Jahrbuch,  Jena,  1908,  Bd. 
xviii,  pp.  285-310): 


Herford,  during  epidemic  at 
Altona,  examined  (cited 
by  Netter  and  Debr6,  loc. 
cit.,  p.  44): 


(a)  39  men  from  a  dormitory  in  which  there  had 
been  several  cases  of  meningitis — found  5 
carriers. 

(6)  29  soldiers  from  the  same  battalion  who  ap- 
plied for  treatment  on  account  of  nasopharyn- 
geal troubles — found  4  carriers. 

(c)  20  men  from  a  regiment  in  which  there  had 
been  no  case  of  meningitis — found  no  carriers. 

(a)  24  persons,  members  of  families  in  which 
there  were  cases  of  meningitis— found  17  car- 
riers. 

(6)  51  school  children  in  a  town  where  there  had 
been  a  recent  case — found  2  carriers,  associ- 
ates of  patient's  sister. 

(c)  10  persons  not  in  contact  with  any  case — 
found  no  carriers. 

(a)  16  men  associated  in  dormitory  with  a  re- 
cent patient — found  10  carriers. 

(6)  114  men  of  the  same  company,  not  room- 
mates of  patient — found  13  carriers. 

(c)  355  men  in  the  3  other  companies  of  same 
garrison — found  19  carriers. 

(d)  Control;  40  men  from  2  battalions  in  Glei- 
witz,  where  there  had  been  no  cases  of  men- 
ingitis— found  no  carriers. 

(a)  387  persons  in  close  contact  with  cases  of 

meningitis — found  28  carriers. 
(6)    127    persons   not   in   contact   with    cases — 

found  no  carriers, 
(c)    184    children    suffering    from   scarlet  fever, 

measles,   whooping-cough    (apparently  unas- 

sociated  with  any  cases  of  meningitis — found 

no  carriers. 

(a)  3154  healthy  persons  in  community  where 
epidemic  prevailed — found  465  carriers. 

(6)  Of  the  above  specimens  were  taken  in  the 
immediate  vicinity,  under  the  investigators' 
supervision,  in  1786  cases — showing  401  car- 
riers. 

(c)  Including  only  members  of  families  in  which 
cases  of  meningitis  had  occurred — 609  were 
examined  and  224  were  found  carriers. 

(d)  Persons  in  the  community  examined  under 
favorable  circumstances  during  and  after  the 
epidemic,  not  directly  associated  with  any 
cases  of  meningitis;  380  examined — 30  found 
carriers. 

172  persons  in  the  families  with  cases  of  menin- 
gitis— found  43  carriers. 


MODE  OF  DISSEMINATION 


59 


Demonstration  of  the  Meningococcus  in  the  Nasopharynx  of  Apparently 
Healthy  Persons — Continued. 


Locality. 

Condition. 

Percent- 
age of 

persons 
exam- 
ined 
shown 
to  be 

carriers. 

Trautmann,    at    Hamburg, 
examined  (cited  by  Net- 
ter  and  Debr6,  loc.  cit.) : 

Mayer,   Waldmann,   Fiirst, 
and     Gruber,     examined 
(Muench.  med.  Wbchen- 
schr.,    1910,    vol.    57,    p. 
1584): 

Kolle  and  Wassermann,  in 
Berlin,  in  1906  (cited  by 
V.    Lingelsheim),    exam- 
ined: 

Droba   and    Kucera,    1906, 
examined   (cited  by  von 
Lingelsheim). 

Kutscher,    1905    (cited    by 
Kelsch,  Rev.  d'Hygiene, 
1911,  vol.  33,  pp.  1-53), 
examined. 

Huber  and  Kutscher  (cited 
by    Kelsch,    Rev.    d'Hy- 
giene, 1911,  vol.  33,  pp. 
1-53),  examined. 

261  persons  in  families  with  cases  of  meningitis 
— found  24  carriers. 

(a)  1911  men  from  various  garrisons  from  1908 
to  1910  at  the  time  of  occurrence  of  cases  of 
meningitis  in  the  respective  garrisons — found 
47  carriers  (associated  with  a  total  of  46  cases 
of  meningitis). 

(6)  in  1910,  at  Munich,  examined  the  whole  gar- 
rison, 9111  men.  It  is  implied  that  there  was 
no  recent  case  of  meningitis  in  the  garrison  at 
this  time,  but  there  had  been  one  or  more 
cases  annually  since  1908  in  each  of  the  bar- 
racks mentioned — 158  of  these  men  were 
found  to  be  meningococcus  carriers. 

114  residents  of  Berlin;  found  2  carriers,  both  of 
whom   had   been   associated   with   suspicious 
cases  of  meningitis — possibly  sporadic  cere- 
brospinal meningitis. 

160  children  in  a  community  free  from  meningi- 
tis— found  no  carriers. 

56  patients  in  Berlin  for  various  affections — 
found  4  carriers. 

A  detachment  of  408  soldiers  free  from  meningi- 
tis both  before  and  after  the  time  of  examina- 
tion— found,,8,carriers. 

9.2 
2.46 

1.73 

1.8 

0.0 
7.4 

2.0 

That  the  number  of  healthy  carriers,  both  in  the 
immediate  vicinity  of  the  patient  and  in  the  general 
community,  runs  parallel  with  the  number  of  persons 
affected  by  the  disease  is  shown  in  the  composite  table 
on  page  GO  from  Brims  and  Holm. 

Similar  results  are  reported  by  Netter  and  Debre, 
who  found  41.00  per  cent,  carriers  in  the  months  of 


60 


MENINGOCOCCUS  MENINGITIS 


March,  April,  and  May,  as  contrasted  with  26.66  per 
cent,  during  June,  July,  and  August. 


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A  point  of  great  importance  in  the  successful 
demonstration  of  the  meningococcus  in  the  naso- 
pharynx is  the  rapidity  with  which  cultures  are  in- 
cubated and  studied.  On  this  point  the  studies  of 
Bruns  and  Holm  are  very  instructive: 

Of  593  specimens  taken  by  them  personally  or  in  their 
presence  and  incubated  immediately,  192  were  positive,  or 
32.4  per  cent. 

Of  1193  specimens  sent  to  them  by  special  messenger, 
209  were  positive,  or  17.5  per  cent. 

Of  1324  specimens  sent  by  mail  within  24  hours,  63  were 
positive,  or  4.7  per  cent. 

Of  30  specimens  sent  by  mail  within  48  hours,  none  were 
positive,  or  0.0  per  cent. 

The  relative  distribution  of  carriers  among  the 
members  of  a  family  was  found  by  Bruns  and  Hohn 
to  be  as  follows: 


MODE  OF  DISSEMINATION  61 

Of  113  fathers  examined  60  were  carriers,  or  53.09  per 
cent. 

Of  114  mothers  examined,  39  were  carriers,  or  34.21  per 
cent. 

Of  360  brothers  or  sisters  examined,  118  were  carriers, 
or  32.77  per  cent. 

Of  22  other  members  examined,  7  were  carriers,  or  32.81 
per  cent. 

The  number  of  carriers  not  only  varies  with  the 
period  of  the  epidemic  and  the  season  of  the  year,  but 
with  the  intimacy  existing  between  the  patient  and  his 
neighbors.  Bochalli  found  10  carriers  among  16 
soldiers  occupying  the  same  barrack  with  a  patient, — 
62.5  per  cent.;  114  soldiers  belonging  to  the  same 
company  yielded  only  13  carriers,  or  11.4  per  cent.; 
19  carriers  were  found  among  355  soldiers  of  the  same 
battalion,  or  5.4  per  cent.  Moreover,  the  hygienic 
surroundings  play  a  determining  role  on  the  number 
of  carriers.  It  has  been  seen  that  epidemics  of  menin- 
gitis occur  most  frequently  in  overcrowded  quarters. 
It  is  but  natural  to  suppose  that  this  is  due  to  the 
greater  number  of  carriers.  Such  indeed  has  been 
found  to  be  the  case.  In  poor  families  Netter  and 
Debre  encountered  31.39  per  cent,  carriers,  while 
among  those  in  comfortable  circumstances  only  15.38 
per  cent,  carriers  were  found.  In  the  mining  districts, 
where  the  miners  work  in  close  proximity  to  each 
other,  the  percentage  of  carriers  is  very  large.     On 


62         MENINGOCOCCUS  MENINGITIS 

the  other  hand,  in  hospitals  the  number  of  carriers 
among  patients,  physicians,  and  nurses  is  almost  nil. 
At  the  New  York  Hospital,  in  which  at  times  there 
are  six  or  seven  meningitis  cases,  repeated  examina- 
tions by  Elser  and  Huntoon  failed  to  reveal  the 
presence  of  carriers  among  patients,  physicians,  or 
nurses.  To  this  is  attributable  the  well-known  fact 
that  instances  of  hospital  contagion  are  so  rare. 

That  the  intensity  of  an  epidemic  runs  parallel 
with  the  number  of  carriers  is  shown  by  the  compara- 
tive statistics  in  Silesia,  Paris,  and  Hamburg  (Netter 
and  Debre).  In  the  very  severe  epidemic  of  Silesia 
in  1904-1905,  with  its  thousands  of  victims,  there  were 
about  327  carriers  in  the  immediate  vicinity  of  each 
patient.  The  moderate  Parisian  epidemic  of  1908- 
1909  gave  only  22.7  per  cent,  carriers.  In  the  com- 
paratively mild  epidemic  at  Hamburg  during  1907, 
in  which  only  93  persons  contracted  the  disease,  only 
9.6  per  cent,  were  found  to  be  carriers. 

Persistence  of  the  Meningococcus  in  the  Naso- 
pharynx of  Healthy  Persons. — Mayer,  Waldmann, 
Fiirst,  and  Gruber  classify  carriers  according  to  the 
persistence  of  meningococci,  as  follows: 

Periodic,  showing  alternate  appearance  and  disappear- 
ance of  the  meningococci. 

Persistent,  in  whom  meningococci  are  constantly  present 
for  weeks  or  months. 


MODE  OF  DISSEMINATION  63 

Temporary,  in  whom  meningococci  are  present  only  for 
a  short  period. 

Of  96  carriers  examined: 

Six  belonged  to  the  periodic  class,  or  6.25  per  cent. 
Twelve  belonged  to  the  persistent  class,  or  12.50  per  cent. 
Sevent}--eight  belonged  to  the  temporary  class,  or  81.25 
per  cent. 

As  a  rule,  the  meningococci  disappear  from  the 
nasophaiynx  of  healthy  persons  within  three  weeks. 
Selter,  however,  obtained  positive  cultures  after  -A  and 
7  months. 

Presence  of  Carriers  among  Individuals  not  Ex- 
posed to  Infection, — The  vast  majority  of  researches 
dealing  with  this  phase  of  the  subject  have  yielded 
negative  results. 

Kolle  and  Wassermann  (112  individuals),  v. 
Lingelsheim  (125  individuals),  Kutscher  (52  in- 
dividuals), and  Goodwin  and  Sholly  (55  first-year 
medical  students)  failed  to  find  carriers  in  individuals 
during  a  time  when  no  epidemic  prevailed  or  in  those 
not  exposed  to  infection.  The  results  of  Mayer, 
Waldmann,  Fiirst,  and  Gruber,  who  found  158 
carriers  among  the  whole  garrison  at  Munich,  con- 
sisting of  9111  men, — i.e.,  1.73  per  cent., — are  unique, 
and  perhaps  attributable  to  the  occurrence  annually 
of  one  or  more  cases  in  each  barrack.   Considering  the 


64         MENINGOCOCCUS  MENINGITIS 

uniformly  negative  results  of  other  observers,  their 
contention  that  the  meningococcus,  like  the  pneumo- 
coccus,  is  almost  ubiquitous  in  the  respiratory  tract 
of  man,  is  hardly  justifiable. 

Distribution  of  the  Meningococcus  in  the  Respira- 
tory Tract. — In  the  earlier  investigations  the  search 
for  the  meningococcus  was  restricted  almost  wholly 
to  the  nasal  mucus.  The  results  were  often  meagre. 
The  bacteriologic  studies  of  v.  Lingelsheim  at  Beu- 
then,  as  well  as  the  post-mortem  results  obtained  by 
Westenhoeffer,  who  found  early  catarrhal  inflamma- 
tion of  the  nasopharynx  in  all  his  cases  of  meningitis, 
soon  led  to  an  important  change  in  the  method  of 
investigation.  Cultures  were  no  longer  taken  from 
the  nose,  but  from  the  nasopharynx  by  the  oral  route, 
with  much  more  satisfactory  results.  While  the 
meningococcus  may  be  found  in  the  tonsils,  in  the 
anterior  and  posterior  nasal  fossa?,  and  even  in  the 
saliva,  its  site  of  election  in  most  cases  is  the  upper 
part  of  the  nasopharynx  and  the  part  of  the  posterior 
nares  in  its  immediate  vicinity. 

The  Local  and  General  Condition  of  Health  of 
the  So-called  "Healthy"  Carriers. — Most  of  the 
carriers  present  no  subjective  or  objective  symptoms, 
and  are  in  fact  in  perfect  health.  Not  so  rarely,  how- 
ever, posterior  rhinoscopy  reveals  the  presence  in 
the  upper  part  of  the  nasopharynx  of  an  inflamed  and 


MODE  OF  DISSEMINATION  65 

reddened  mucous  membrane  covered  with  a  viscid 
mucopurulent  secretion.  Still  more  rarely  the  menin- 
gococcus betrays  its  presence  by  a  severe  coryza,  which 
may  last  2  to  3  days  or  several  weeks.  Even  in  the 
presence  of  an  inflammation  of  the  nasopharynx  there 
is  almost  never  any  complaint  of  local  pain  or  diffi- 
culty in  swallowing.  In  exceptional  cases  there  may 
be  slight  transitory  febrile  movement,  associated  with 
slight  malaise,  and  mild  headache.  These  cases  are 
perhaps  the  connecting  links  between  perfectly 
healthy  carriers  and  abortive  forms  of  meningitis  or 
meningococcic  sepsis  without  involvement  of  the 
meninges. 

Source  of  the  Meningococcus  found  in  the  Naso- 
pharynx of  Meningitis  Patients. — It  is  conceivable 
that  the  meningococcus  may  come  from  one  of  two 
sources, — namely,  from  the  external  world  by  inhala- 
tion of  contaminated  air  or  from  the  infected  meninges 
by  way  of  the  lymphatics  at  the  base  of  the  brain. 
For  the  first  source  nearly  all  the  data  previously 
adduced  speak,  such  as  the  early  appearance  and 
rapid  disappearance  of  the  meningococci,  the  presence 
of  meningococci  before  the  onset  of  meningeal  symp- 
toms, and  the  analogy  with  healthy  germ  carriers 
where  the  atmospheric  source  is  the  only  possible  one. 
That  some  of  the  meningococci  may  come  from  the 
meninges  by  way  of  the  lymph-channels  is  suggested 

5 


66         MENINGOCOCCUS  MENINGITIS 

by  the  finding  of  Gram-negative  cocci  in  the  naso- 
pharynx of  monkeys  suffering  from  experimental 
meningitis.  Unfortunately,  Flexner,  who  made 
these  observations,  did  not  identify  the  organisms  in 
cultures.  The  occasional  reappearance  of  meningo- 
cocci in  the  throat  of  patients  during  an  exacerba- 
tion at  a  late  stage  of  the  disease,  as  observed  by 
Elser  and  Huntoon,  would  also  speak  for  this 
assumption.  In  experimental  poliomyelitis,  the 
passage  of  the  virus  from  the  brain  to  the  mucous 
membrane  of  the  upper  respiratory  tract  has  been 
repeatedly  proved. 

Mode  of  Contagion. — The  data  drawn  from  epi- 
demiologic and  bacteriologic  studies  justify  the  con- 
clusion that  the  usual  mode  of  transmission  of  the 
disease  is  directly  from  one  individual  to  another. 
This  does  not  necessarily  mean  that  transmission  is 
from  patient  to  patient.  Indeed  there  is  reason  to 
believe  that  in  most  cases  the  source  of  contagion  is  a 
healthy  or  apparently  healthy  meningococcus  carrier. 
As  we  have  seen,  it  has  been  estimated  that  there  are 
ten  to  twenty  times  as  many  carriers  as  there  are 
patients.  Moreover,  individuals  suffering  from 
meningitis  are  confined  to  bed,  thus  limiting  the 
number  of  persons  with  whom  they  come  in  contact. 
The  somnolent  or  apathetic  condition  of  many  of  the 
patients  also  lessens  the  danger  of  transmission  of  the 


MODE  OF  DISSEMINATION  67 

disease  by  expectoration  of  germ-laden  sputum.  In 
the  cases  of  patients  in  the  period  of  childhood  there 
is  still  less  likelihood  of  the  disease  being  transmitted, 
as  most  of  these  swallow  their  sputum.  The  strange 
fact  that  cases  of  hospital  contagion  are  so  rare  is 
probably  due  to  the  greater  number  of  meningitis 
patients  in  these  institutions  being  children.  In  the 
few  instances  where  the  source  of  contagion  could  be 
traced  to  inmates  suffering  from  meningitis,  the 
patients  were  adults.  The  question  has  been  raised 
whether  the  meningococci  found  in  the  throat  of 
healthy  germ  carriers  are  not  attenuated  or  avirulent 
forms  of  the  organisms.  By  experimental  studies  it 
is  rather  difficult  to  determine  the  answer  to  this 
question.  We  have  seen  how  feeble  and  inconstant 
is  the  pathogenicity  of  this  organism  for  the  ordinary 
laboratory  animal.  However,  the  occurrence  of 
meningitis  in  persons  subsequent  to  their  having  been 
proved  to  be  carriers,  as  reported  by  Stuhlen,  Bruns 
and  Hohn,  and  Bochalli,  shows  that  at  least  in  these 
cases  the  organism  was  virulent  to  the  extent  of  being 
capable  of  producing  an  infection  of  the  meninges. 

It  is  probable  that  transmission  of  the  disease 
occurs  most  frequently  through  the  medium  of  minute 
particles  of  moisture  (droplets  of  Fliigge)  derived 
from  the  respiratory  tract  of  an  individual  harboring 
the  meningococcus.     It  is  possible  that  conveyance 


68         MENINGOCOCCUS  MENINGITIS 

of  infection  may  also  occur  by  hand-shaking,  kissing, 
the  use  of  common  eating  or  drinking  utensils,  same 
handkerchiefs  or  towels,  or  food  contaminated  by 
soiled  fingers.  For  the  preservation  of  the  patho- 
genic power  of  the  infective  material  it  is  necessary 
that  the  time  elapsing  between  its  elimination  and 
reception  should  be  short.  Indirect  contagion  through 
the  agency  of  inanimate  objects,  though  possible,  is 
not  likely.  The  low  degree  of  viability  of  the  menin- 
gococcus outside  of  the  human  body  speaks  against 
this  assumption.  At  any  rate,  such  a  mode  of  trans- 
mission of  the  disease  has  thus  far  not  been  proved. 

The  great  number  of  meningococcus  carriers  dur- 
ing the  epidemic  incidence  of  meningitis  show  the 
great  receptivity  of  the  human  body  for  the  meningo- 
coccus at  such  a  period.  There  is,  however,  a  marked 
difference  between  receptivity  and  susceptibility  to 
meningeal  infection.  Most  of  those  individuals  that 
become  meningococcus  carriers  escape  infection.  It 
is  only  a  comparatively  small  number  who,  as  a  result 
of  local  or  general  susceptibility,  succumb  to  infection. 
The  nature  of  the  barriers  that  prevent  the  passage 
of  the  meningococcus  beyond  the  boundaries  of  the 
mucous  membrane  of  the  respiratory  tract  is  not 
known.  We  merely  know  that  in  children  and  in- 
dividuals  living  under   unhygienic  conditions   they 


MODE  OF  DISSEMINATION  69 

offer  less  resistance  to  the  invasion  of  the  meningo- 
coccus. 

The  high  degree  of  receptivity  and  low  degree  of 
susceptibility  to  meningeal  infection  exhibited  by  the 
human  body  toward  the  meningococcus  explain  some 
of  the  bizarre  features  encountered  in  the  study  of  the 
epidemiology  of  the  disease,  such  as  the  propagation 
by  leaps  and  bounds  and  the  simultaneous  outbreak 
in  localities  far  removed  from  one  another. 

Causes  of  Epidemic  Outbreaks. — Theoretically 
there  are  only  two  possible  factors  that  can  enter, 
alone  or  in  combination,  in  the  causation  of  an  epi- 
demic,— namely : 

Sudden  increase  in  virulence  of  the  specific 
organism. 

Sudden  general  increase  in  susceptibility  to  infec- 
tion by  the  specific  organism. 

The  possibility  of  a  rapid  enhancement  of  diffusi- 
bility  of  the  organism  should  be  borne  in  mind.  Even 
if  such  a  phenomenon  were  demonstrable  in  every 
epidemic,  it  could  on  further  analysis  be  shown  to  be 
dependent  upon  one  or  the  other  of  the  two  factors 
Darned  above.  Rapid  diffusibility,  however,  can  not 
possibly  explain  the  simultaneous  appearance  of  epi- 
demics in  parts  thousands  of  miles  distant  from  one 
another.     Yet  such  outbreaks  have  been  repeatedly 


70        MENINGOCOCCUS  MENINGITIS 

observed  from  the  very  earliest  history  of  meningo- 
coccus meningitis. 

Experimental  work,  with  the  exception  of  that  of 
Ruppel  which  remains  unconfirmed,  has  failed  to 
produce  an  increase  in  the  virulence  of  the  meningo- 
coccus by  any  method  known  to  bacteriology.  Nor 
has  it  been  shown  that  strains  of  the  meningococcus 
cultivated  from  patients  during  an  epidemic  are  regu- 
larly more  virulent  than  those  derived  from  sporadic 
cases. 

The  existence  of  a  general  decrease  in  human 
resistance  to  meningococcic  infection  is  still  less  sus- 
ceptible of  scientific  proof,  as  experimental  demon- 
stration is  out  of  the  question.  The  increased  inci- 
dence of  other  contagious  diseases  during  outbreaks 
of  epidemic  meningitis  should  lead  us  to  assume  the 
temporary  appearance  of  a  common  factor.  It  is  less 
difficult  to  conceive  of  a  general  decrease  in  resistance 
to  infections  than  of  a  sudden  and  simultaneous  in- 
crease in  virulence  of  a  number  of  organisms. 

In  pandemic  outbreaks  a  cosmic  factor — such  as 
change  in  climatic  conditions — must  necessarily  be 
present,  but  at  present  it  is  entirely  a  matter  of  con- 
jecture whether  its  action  is  directly  in  increasing  the 
virulence  of  the  meningococcus  or  the  susceptibility  of 
the  human  body. 

Mode  of  Invasion  of  the  Meninges  by  the  Menin- 


MODE  OF  DISSEMINATION  71 

gococcm. — While  practical  unanimity  has  been 
reached  regarding  the  usual  portal  of  entry  of  the 
organisms  in  the  body,  opinions  are  still  divided  on 
the  question  of  the  mode  of  invasion  of  the  meninges. 
The  proximity  of  the  roof  of  the  nasopharynx  to  the 
base  of  the  brain  naturally  suggests  the  likelihood  of 
direct  penetration  of  the  meningococcus  along  the 
structures  in  this  region.  Support  was  lent  to  this 
assumption  by  the  early  pathologic  studies.  Westen- 
hoeffer  found  constant  redness,  swelling,  and  hyper- 
secretion of  the  mucous  membrane  of  the  nasopharynx 
and  practically  constant  involvement  of  the  sphe- 
noidal sinuses.  This  observer,  in  common  with  others, 
found  the  first  traces  of  exudate  in  the  region  of  the 
optic  chiasm  and  hypophysis, — i.e.,  structures  con- 
tiguous to  the  sphenoidal  sinuses.  But  a  more  careful 
study  of  his  material  soon  led  Westenhoeffer  to 
abandon  his  earlier  view, — that  the  meningococcus 
gains  access  to  the  meninges  by  direct  extension.  The 
perihypophyseal  inflammation  was  confined  to  the 
superior  and  lateral  surfaces,  which  would  not  be  the 
case  if  the  invasion  occurred  by  direct  extension  along 
the  sphenoid  bone.  Moreover,  sections  through  this 
bone  failed  to  reveal  either  the  presence  of  the  menin- 
gococcus or  evidence  of  inflammatory  changes  in  the 
deeper  portions.  Similarly  there  is  no  histological 
evidence  of  the  spread  of  the  inflammatory  process 


72         MENINGOCOCCUS  MENINGITIS 

along  the  cranial  and  spinal  nerves  and  the  lymphatics 
around  the  carotid. 

There  being  no  anatomical  proof  for  the  sphe- 
noidal route,  two  other  modes  of  direct  invasion  re- 
main to  be  considered, — namely,  the  trans-ethmoidal 
and  the  aural  route.  Cuneo  and  Andre  claim  to  have 
found  in  the  cribriform  plate  of  the  ethmoid  a  system 
of  anastomosing  canalicules  which  in  the  infant  com- 
municate directly  with  the  subarachnoid  space  at  the 
base  of  the  brain.  It  has  been  proved  that  the  circula- 
tion of  lymph  in  this  region  is  from  the  base  of  the 
brain  outward  toward  the  nasopharynx.  It  has  been 
assumed  by  a  number  of  observers  that  the  meningo- 
coccus traverses  this  region  in  the  opposite  direction. 
But  in  the  human  infection  at  least,  neither  Macken- 
zie and  Martin  nor  Netter  and  Debre  have  succeeded 
in  demonstrating  the  meningococcus  in  any  part  of 
the  ethmoid  bone.  In  experimental  meningitis,  Gram- 
negative  diplococci  were  found  by  Flexner  in  this 
region.  But,  as  infection  occurred  by  intradural  in- 
fection, the  organisms  were  evidently  in  the  process 
of  being  excreted.  There  is  consequently  no  direct 
proof  of  the  trans-ethmoidal  invasion  of  the  menin- 
gococcus. 

That  the  infection  extends  along  the  Eustachian 
tubes  and  middle  and  internal  ears  is  unlikely,  by  rea- 
son of  the  fact  that  in  most  of  the  cases  there  is  no 


MODE  OF  DISSEMINATION  73 

evidence  of  early  inflammation  of  the  middle  ear. 
The  validity  of  the  argument  in  favor  of  direct  ex- 
tension from  the  nasopharynx,  by  reason  of  the 
alleged  appearance  of  the  exudate  first  at  the  base  of 
the  brain,  loses  its  whole  force  when  we  consider  that 
a  similar  localization  takes  place  in  tuberculous  menin- 
gitis, in  which  the  infecting  organism  undoubtedly 
reaches  the  meninges  by  the  blood  stream.  Similarly 
in  experimental  meningitis,  produced  by  intradural 
infection  of  the  meningococcus,  the  primary  site  of 
the  exudate  is  also  found  at  the  base  of  the  brain. 
Moreover,  Busse  has  demonstrated  that  the  exudate 
appears  simultaneously  at  the  base  of  the  brain  and 
in  the  spinal  meninges. 

The  recent  successful  cultivation  of  the  virus  of 
poliomyelitis  in  the  form  of  a  microscopically  visible 
organism  brings  poliomyelitis  and  meningitis  into 
closer  relationship.  In  both  the  specific  causative 
agent  has  a  special  affinity  for  the  tissues  of  the 
central  nervous  system.  Moreover,  in  both  diseases 
the  mucous  membrane  of  the  nasopharynx  seems  to 
be,  in  the  vast  majority  of  the  cases,  the  primary  portal 
of  entry.  So  that  the  facts  established  regarding  the 
mode  of  invasion  of  the  central  nervous  system  by 
the  virus  of  poliomyelitis  should  have  some  bearing 
on  the  problem  of  the  meningococcus  invasion  of  the 
meninges.    Flexner  has  shown  that  when  a  monkey  is 


74        MENINGOCOCCUS  MENINGITIS 

killed  forty-eight  hours  after  an  intranasal  inoculation 
of  the  virus,  and  the  brain,  spinal  cord,  and  olfactory 
lobes  separately  inoculated  into  other  monkeys,  in- 
fection is  produced  by  the  olfactory  lobes  only.  This 
proves  that  the  virus  had  not  in  this  brief  period 
reached  the  more  distant  parts  of  the  central  nervous 
system,  and  that  the  infection  is  an  ascending  one 
along  the  olfactory  filaments.  Unfortunately,  in  the 
case  of  meningitis  no  one  has  as  yet  succeeded  in  pro- 
ducing the  disease  in  animals  by  intranasal  inocula- 
tion. Were  this  possible,  the  question  of  the  mode 
of  invasion  would  probably  receive  its  immediate  solu- 
tion. In  brief,  at  the  present  time  there  are  no  direct 
facts  in  support  of  the  assumption  that  the  meninges 
are  invaded  by  direct  ascension  of  meningococcus 
from  the  nasopharynx. 

On  the  other  hand,  a  number  of  facts  speak  for 
the  primary  invasion  of  the  blood  and  secondary  in- 
fection of  the  meninges.  Blood  cultures  have  been 
positive  in  about  one-third  of  the  cases  examined,  and 
it  is  probable  that  with  improvement  in  technic  posi- 
tive results  will  become  more  frequent.  However, 
only  the  results  obtained  in  the  earliest  period  of  the 
disease  have  any  bearing  on  this  question.  Salomon, 
Martini  and  Rohde,  Marcovitz,  and  Andrewes  have 
demonstrated  the  meningococcus  in  the  blood  previ- 
ous   to    the    appearance    of    pronounced    meningeal 


MODE  OF  DISSEMINATION  75 

symptoms.  At  autopsy,  lesions  in  the  heart  and  other 
viscera  have  been  found  in  individuals  that  died  within 
twenty-four  hours  of  the  onset  of  the  disease.  Not 
infrequently  characteristic  eye  symptoms  have  been 
found  that  were  in  the  same  stage  as  those  of  the 
central  nervous  system.  On  the  other  hand,  it  must 
be  admitted  that  in  most  of  these  cases  the  clinical 
course  was  dominated  by  the  septic  process,  and 
differed  considerably  from  that  of  the  ordinary  type 
of  meningococcus  meningitis.  Moreover,  in  the  ma- 
jority of  the  cases,  but  few  organisms  could  be 
isolated,  indicating  a  transient  invasion  of  the  blood 
stream. 

Elser  and  Huntoon  consider  the  sudden  onset  an 
argument  in  favor  of  the  primary  invasion  of  the 
blood.  In  otogenic  and  traumatic  meningitis,  in 
which  local  infection  of  the  meninges  is  likely,  the 
symptoms  develop  more  gradually  and  irregularly. 

Solution  of  this  difficult  problem  is  apparently 
only  to  be  attained  by  animal  experimentation. 
Unfortunately,  so  far  all  attempts  to  produce  a  char- 
acteristic meningitis  in  animals  by  intranasal,  intra- 
pharyngeal,  or  intravenous  inoculation  of  the  menin- 
gococcus have  resulted  in  complete  failure.  The 
intradural  production  of  meningitis,  which  has  suc- 
ceeded in  the  hands  of  v.  Lingelsheim  and  Leuchs, 
Flexner,  Stuart  McDonald,  and  others,  does  not  aid 


76         MENINGOCOCCUS  MENINGITIS 

us  in  the  solution  of  this  question.  By  injecting 
intravenously  an  organism  closely  resembling  the 
streptococcus  mucosus,  Elser,  Huntoon,  and  Strauss 
succeeded  in  producing  a  meningitis  in  rabbits,  which 
in  its  sudden  onset  after  a  latent  period  of  several  days 
resembled  closely  the  disease  in  man.  The  present 
state  of  our  knowledge  permits  us  to  state  that  there 
is  some  evidence,  but  no  conclusive  proof,  that  the 
meningococcus  primarily  invades  the  blood  and 
secondarily  the  meninges. 

Bibliography 

Kiefer:    Berl.  klin.  Wochenschr.,  1896,  xxxiii,  628. 
Councilman,  Mallory  and  Wright:     Report  of  State  Board 

of  Health,  Mass.,  Boston,  1898. 
Albrecht   and   Ghon:    Wiener  klin.   Wochenscr.,   1901,   xiv, 

984. 
Salomon:     Berl.  klin.  Wochenschr.,  1902,  xxxix,  1045. 
Lord:    Centr.  f.  Bakt.  u.  Parasit.,  Orig.,  1903,  xxxiv,  641. 
Weichselbaum :     Kolle   and  Wassermann   Handbuch,   1903, 

iii,  256. 
Martini  and  Rohde:    Berl.  klin.  Wochenschr.,  1905,  xiii,  997. 
v.  Lingelsheim:    Klin.  Jahrbuch,  1906,  xv,  Heft  2,  373. 
Goodwin  and  Sholly:    Jour.  Infect.  Dis.,  1906,  Suppl.  ii,  21. 
Fliigge:    Klin.  Jahrbuch,  1906,  xv,  Heft  2. 
Andrewes:    Lancet,  1906,  ii,  1172. 
Dieudonne:      Centr.    Bakt.    u.    Parasit.,    1906,   xli,    1    Abt., 

Orig.,  418. 
Osterman :    Deut.  med.  Wochenschr.,  1906,  xxxii,  414. 


MODE  OF  DISSEMINATION  77 

Marcovitz:     Wiener  klin.  Wochenschr.,  1906,  xix,  1312. 
Flexner:    Jour.  Exper.  Med.,  1907,  ix,  142. 
Bochalli :    Zeit.  f .  Hyg.  u.  Infect.,  1908,  lxi,  454. 
Duval :    Jour.  Med.  Research,  1908,  xix,  N.S.  xiv,  258. 
v.  Lingelsheim:    Zeit.  f.  Hyg.  u.  Infect.,  1908,  lix,  457. 
Bruns  and  Hohn :     Klin.  Jahrbuch,  1908,  xviii,  285. 
Trautman  and  Fromme:     Muench.  med.  Wochenschr.,  1908, 

lv,  791. 
Herford:    Klin.  Jahrbuch,  1908,  xix,  265. 
Selter:    Klin.  Jahrbuch,  1909,  xx,  457. 
Elser  and  Huntoon :    Jour.  Med.  Research,  1909,  xx,  377. 
Mayer,    Waldmann,    Fiirst    and    Gruber:      Muench.    med. 

Wochenschr.,  1910,  lvii,  1584. 
Netter  andDebi-c:  La  Meningite  Cerebrospinale,  Paris,  1911. 
Frost:    Pub.  Health  Bull.,  1912,  xxvii,  97. 


CHAPTER  V 

Pathologic  Anatomy 

Before  proceeding  with  the  description  of  the 
pathologic  anatomy  of  this  disease,  it  seems  desirable 
to  recall  some  features  of  the  anatomy  of  the  meninges 
and  central  nervous  system  which  are  important  in 
this  connection.  While  some  anatomists  describe  two 
membranes,  the  pia-arachnoid  and  dura,  it  seems  best 
for  our  purpose  to  divide  the  meninges  into  three, — 
namely,  pia  mater,  arachnoid,  and  dura  (Fig.  8). 
The  pia  is  a  delicate  membrane  composed  chiefly  of 
blood-vessels  which  penetrate  the  substance  of  the 
central  nervous  system  at  innumerable  points.  It 
forms  the  visceral  layer  of  the  leptomeninges,  and 
follows  closely  the  irregularities  of  the  surface  of 
the  brain  and  cord,  dipping  into  the  sulci  and  pro- 
jecting into  the  ventricles  in  the  form  of  a  network 
of  capillaries  which  are  known  as  the  choroid  plex- 
uses. These  capillaries  are  lined  by  a  layer  of  epithe- 
lium, which  probably  plays  an  important  part  in  the 
secretion  of  cerebrospinal  fluid.  The  arachnoid  is  the 
outer  of  the  two  leptomeninges.  It  follows  more 
closely  the  reflections  of  the  inner  layer  of  the  dura 
and  is  in  part  only  loosely  connected  with  the  pia 
mater  by  means  of  delicate  septa. 

78 


Dura  mater 
sArachnoidea 
,,Pja  mater 


-rouria  ventricle 


C.  sterna  magna 
Foramen  Magendii 


Subdural  space 
Subaractinoid  space 

Shcra  ing  membranes  covering  1  >r;ii n  and  location  of  cisterna. 


PATHOLOGIC  ANATOMY  79 

It  does  not  dip  into  the  sulci.  At  the  base  and 
lateral  aspect  of  the  brain  there  is  distinct  separation 
between  the  pia  and  arachnoid,  leaving  a  number  of 
quite  large  spaces  which  bear  the  name  of  cisterna. 
The  most  important  of  these  are  the  cisterna  chias- 
matis,  basalis,  pontis,  and  cerebello-medullaris  or 
cisterna  magna.  They  form  intercommunicating 
portions  of  the  subarachnoid  space  at  the  base  of 
the  brain.  The  cisterna  magna  communicates  freely 
with  the  fourth  ventricle  through  the  mediation  of  the 
median  foramen  of  Magendie  and  the  lateral  fora- 
mina of  Key  and  Retzius  or  Luschka.  It  drains  into 
the  subarachnoid  space  of  the  spinal  canal. 

The  spinal  arachnoid  lines  the  inner  surface  of  the 
dura  throughout  its  whole  extent,  while  the  pia  closely 
invests  the  spinal  cord,  thus  leaving  a  considerable 
space  between  the  two  membranes.  Through  this 
space  pass  many  slender  bands  and  trabecular  which 
connect  the  pia  with  the  arachnoid.  In  the  vicinity 
of  the  pia  these  trabecular  greatly  increase  in  number. 
In  this  region  there  is  found  a  delicate  fenestrated 
membrane  running  the  whole  length  of  the  cord, 
which  partly  shuts  off  the  space  along  its  inner  sur- 
face, known  as  the  epi-pial  space,  from  the  general 
subarachnoid  space.  This  accounts  for  the  fact  that 
occasionally  a  comparatively  clear  fluid  is  obtained 
on  lumbar  puncture  in   cases  where  a  subsequent 


80 


MENINGOCOCCUS  MENINGITIS 


autopsy  shows  the  cord  enmeshed  in  a  thick  exudate. 
The  subarachnoid  space  is  further  subdivided  into  an 
anterior  and  a  posterior  half  by  the  ligamentum 
denticulatum. 


SUBDURAL 
SPACE 


FORAMEN  OF 
MAJENDIt. 


ONE  OF  THE  LATERAL 
FORAMINA  OF  LUSCHKAt 


Fig.  9. — Showing  ventricular  system  of  brain  and  foramina  of  4th  ventricle.     (Still.) 

The  ventricular  system  ( Fig.  9 )  of  the  brain  con- 
sists of  the  lateral  ventricle  in  each  cerebral  hemi- 
sphere; the  third  ventricle,  situated  between  the  two 
hemispheres  and  connected  with  the  former  by  means 
of  the  foramina  of  Monro;  and  the  fourth  ventricle, 
lying  between  the  cerebellum,  pons,  and  medulla, 
and  communicating  with  the  third  ventricle  by  means 


PLATE  I 


Macroscopic  lesions  of  convexity  of  lirain  meningococcus  meningitis.     I  ECoplik. 


PLATE  II 


Side  view  of  brain  meningococcus  meningitis.     (Koplik.) 


PATHOLOGIC  ANATOMY  81 

of  a  narrow  channel,  the  aqueduct  of  Sylvius.  The 
fourth  ventricle  is  directly  continuous  with  the  central 
canal  of  the  cord. 

Macroscopic  Appearance  of  the  Meninges  and 
Central  Nervous  System  in  the  Acute  Stage  (Plates 
I  and  II.) — The  macroscopic  lesions  of  the  central 
nervous  system  in  this  disease  are  not  characteristic. 
They  differ  but  little  from  the  changes  seen  in  other 
forms  of  acute  suppurative  meningitis.  The  dura  is 
tense  and  at  times  its  vessels  show  considerable  injec- 
tion. Its  inner  surface  is  shining,  and  small  hemor- 
rhages may  be  present  in  those  portions  which  cover 
the  base  of  the  brain.  On  opening  the  dura,  a  con- 
siderable amount  of  turbid  fluid  or  pus  may  escape 
from  the  subarachnoid  space.  The  picture  presented 
varies  greatly  with  the  acuteness  and  severity  of  the 
infectious  process.  In  some  cases  a  purulent  exudate 
forms  within  twenty-four  hours  from  the  onset  of  the 
disease;  in  others  pus  is  not  found  in  the  first  few 
days. 

In  fulminating  cases  there  is  intense  injection  of 
the  blood-vessels  of  the  leptomeninges,  at  times  giving 
a  pinkish  hue  to  the  entire  surface  of  the  brain.  The 
brain  seems  to  be  increased  in  volume,  as  evidenced 
by  flattening  of  the  gyri.  The  normal  transparency 
and  shimmer  of  the  meninges  are  lost.  In  the  sulci 
a  small  quantity  of  turbid  fluid  is  usually  seen  on  the 

G 


82         MENINGOCOCCUS  MENINGITIS 

convexity  of  the  brain.  At  the  base,  especially  in  the 
vicinity  of  the  hypophysis,  there  is  often  present  a 
small  collection  of  pus. 

In  cases  of  less  severity,  where  death  has  taken 
place  in  from  five  to  ten  days,  the  exudate  is  more 
abundant.  It  is  yellowish-green,  thick,  and  gelatin- 
ous. It  is  most  abundant  at  the  base  and  in  the  sulci 
Of  the  convexity  of  the  brain,  where  it  is  seen  as  more 
or  less  isolated  bands  and  plaques  along  each  side  of  a 
congested  blood-vessel.  In  more  advanced  cases 
there  is  present  at  times  a  cap  of  pus  of  considerable 
thickness  covering  the  upper  and  lateral  surface  of 
the  frontal  lobe  and  the  anterior  half  of  the  parietal 
lobes.  This  peculiar  localization  of  the  exudate  is 
attributed  by  Goeppert  to  the  distribution  of  the 
anterior  and  middle  cerebral  arteries.  The  greater 
abundance  of  the  exudate  at  the  base  is  due  not  so 
much  to  the  effect  of  gravity,  but  to  the  fact  that  in 
this  region  the  subarachnoid  space  is  more  voluminous 
and  the  membranes  have  larger  meshes.  At  the  base 
the  exudate  accumulates  first  in  the  region  of  the 
optic  chiasm,  hypophysis,  and  tuber  cinereum.  From 
here  it  spreads  anteriorly  along  the  optic  nerves, 
laterally  over  the  lateral  aspects  of  the  frontal  and 
parietal  lobes,  and  posteriorly  over  the  inferior  sur- 
faces of  the  pons,  medulla  and  cerebellum,  and  the 
cisterna  magna.     Having  reached   this  region,   the 


PATHOLOGIC  ANATOMY  83 

exudate  flows  along  the  cerebral  peduncles  and  the 
furrow  between  the  parietal  lobe,  pons,  and  cere- 
bellum, and  then  covers  the  superior  vermiform  pro- 
cess and  upper  surfaces  of  the  lobes  of  the  cerebellum. 

On  exposure  of  the  membranes  of  the  cord,  the 
dura  is  found  distended.  Its  vessels  are  markedly 
injected,  and  the  fat  lobules  usually  found  along  its 
outer  surface  often  show  small  hemorrhagic  extra- 
vasations and  occasionally  purulent  infiltration. 
There  is  marked  congestion  of  the  vessels  on  the  inner 
surface  of  the  dura.  At  times  there  are  seen  small 
ecchymoses  and  fibrinous  plaques.  The  exudate, 
which  is  confined  almost  wholly  to  the  posterior  aspect 
of  the  leptomeninges,  usually  appears  about  the  same 
time  as  in  the  meninges  of  the  brain.  It  is  most 
abundant  in  the  cervical,  lower  dorsal,  and  lumbar 
regions.  The  parts  of  the  meninges  free  from  exudate 
show  a  loss  of  the  normal  lustre  and  transparency. 
There  is  visible  injection  of  the  blood-vessels  of  the 
anterior  surface  of  the  meninges.  Rarely  is  a  puru- 
lent exudate  present  in  this  region. 

The  ventricles  in  the  first  days  of  the  disease  show 
little  change.  Soon  thereafter  they  become  some- 
what dilated,  and  are  filled  with  a  turbid  fluid  con- 
taining fibrinous  flocculi.  The  ependymal  lining  be- 
comes   lustreless.      The    choroid    plexus    is    at    first 


84         MENINGOCOCCUS  MENINGITIS 

hyper^emic,  later  it  assumes  a  dull  grayish  appear- 
ance. 

The  parenchyma  of  the  brain  and  cord  shows  few 
lesions  which  are  apparent  to  the  naked  eye.  The 
inflammation  is  sharply  limited  to  the  meninges  which 
are  readily  stripped  off  from  the  brain  tissue.  The 
vessels  of  the  gray  and  white  substance  are  injected, 
and  the  cortex  seems  to  be  cedematous.  Punctiform 
hemorrhages  have  been  seen  more  frequently  by  some 
observers  than  by  others.  Distinct  areas  of  softening- 
are  rare,  while  abscess  formation  is  still  more  rare. 
Hemorrhagic  foci  are  less  often  seen  in  the  cord  than 
in  the  brain. 

Chronic  Stage. — The  exudate  at  the  convexity 
usually  disappears  within  fifteen  to  thirty  days.  It  is 
replaced  by  local  or  general  thickening  of  the 
meninges.  Yellowish-white,  dense,  and  opaque  bands 
are  usually  seen  along  the  vessels  at  the  convexity. 
At  the  base  dense  adhesions  are  still  more  often  seen. 
False  cysts  may  be  formed  containing  clear,  turbid, 
or  purulent  fluid,  producing  so-called  sacculated 
meningitis.  In  stripping  off  the  membranes  small 
portions  of  the  cortex  are  often  torn  away.  In  places 
the  leptomeninges  may  become  adherent  to  the  dura. 

The  meninges  of  the  cord  show  similar  thicken- 
ings, but,  as  a  rule,  they  are  less  general  and  marked 
than  in  the  meninges  of  the  brain.    They  are  almost 


PATHOLOGIC  ANATOMY  85 

always  confined  to  the  posterior  aspects  of  the  cord. 
The  spinal-nerve  roots  may  be  embedded  in  a  net- 
work of  false  membrane.  After  convalescence  has 
become  established  the  adhesions  are  for  the  most  part 
absorbed.  Autopsy  at  this  period  may  reveal  an 
isolated  opaque  plaque  here  and  there. 

The  ventricles  in  the  chronic  stage  are  usually 
markedly  dilated.  The  ependyma  is  thickened  and 
irregular.  Its  lining  membrane  has  partly  disap- 
peared. It  is  covered  with  granulations  which  are 
adherent  to  the  underlying  brain  tissue.  The  sub- 
ependymal tissue  is  more  reticular  and  oedematous. 
Pus  is  often  present  in  the  more  dependent  portions 
of  the  posterior  and  inferior  cornua,  at  a  time  when 
it  has  completely  disappeared  from  the  surface  of  the 
brain.  False  membrane  may  at  times  obliterate  the 
communications  between  the  various  ventricles.  The 
studies  of  Goeppert  show  that  complete  obliteration 
is  not  as  frequent  as  it  is  usually  thought  to  be.  In 
most  of  the  cases  studied  by  him,  he  demonstrated  a 
free  flow  of  injected  fluid  from  the  ventricles  into  the 
spinal  subarachnoid  space. 

The  parenchyma  of  the  brain  and  cord  shows 
practically  no  changes  that  are  apparent  to  the  naked 
eye. 

Microscopic  Lesions.  Acute  Stage.— The  essen- 
tial morbid  process  is  a  purulent  infiltration  of  the 


86        MENINGOCOCCUS  MENINGITIS 

leptomeninges.  The  question  of  the  primary  seat  of 
the  meningeal  inflammation  is  still  an  open  one. 
WestenhoefFer  contends  that  the  inflammation  is 
primarily  localized  in  the  arachnoid,  that  the  disease 
is  a  suppurative  arachnitis.  He  bases  this  assumption 
chiefly  on  the  fact  that  in  the  depths  of  the  sulci 
where  the  pia  alone  is  present,  the  inflammatory 
changes  are  less  marked  than  in  the  more  superficial 
portions.  The  earliest  lesions  are  seen  in  the  vicinity 
of  the  blood-vessels  which  are  markedly  dilated.  In 
the  walls  and  within  the  lumina  of  the  smaller  veins 
are  present  many  leucocytes.  At  times  there  is  evi- 
dence of  thrombophlebitis.  Gradually  the  leucocytic 
infiltration  of  the  meninges  becomes  more  general, 
the  fine  trabecule  and  septa  of  the  arachnoid  dis- 
appear, and  larger  and  smaller  spaces  are  formed  con- 
taining masses  of  inflammatory  cells.  Between  the 
cells  there  is  present  a  fine  granular  material  repre- 
senting the  coagulated  serum  of  the  exudate.  There 
is  little  fibrin  in  the  early  stages  of  the  disease.  In  the 
exudate  the  cell  masses  are  larger  and  more  abundant. 
The  exudate  chiefly  contains  four  kinds  of  cells.  The 
predominant  cells  are  polymorphonuclears,  either 
normal  in  appearance  or  degenerated.  The  lympho- 
cytes are  less  abundant.  In  addition  to  these  there 
are  present  large  cells  from  two  to  eight  times  the  size 
of  a  polymorphonuclear  cell,  having  a  faintly  stained, 


PLATE 


<r'V 


-    MS  V 


..-     '*3>* 


^  j.  % 

-. 

\ 


Lesions  ol  apinal  cord  meningococua  meningitia,  adull  case  I  Koplik  i 


PATHOLOGIC  ANATOMY  87 

finely  granular  protoplasm,  and  a  large  eccentric 
vesicular  nucleus.  They  often  contain  a  number  of 
ingested  cells  lying  in  vacuoles  of  the  protoplasm. 
Their  number  varies  considerably.  They  were  first 
described  in  1865  by  Boehmer,  who  considered  them 
to  be  the  mother  cells  of  the  pus-cells  which  were  seen 
in  them.  Councilman,  Mallory  and  Wright  have  been 
able  to  follow  the  various  steps  of  their  formation 
from  the  connective-tissue  cells  of  the  meninges.  They 
may  also  arise  from  the  adventitia  of  the  blood-vessels. 
They  have  been  demonstrated  in  other  forms  of 
meningitis.  Red  blood-cells  are  present  in  variable 
quantities.  As  a  rule  they  are  seen  in  great 
numbers.     Eosinophils  are  almost  never  present. 

The  changes  in  the  meninges  of  the  cord  (Plate 
III)  are  similar  to  those  of  the  meninges  of  the  brain. 
The  large  cells,  described  above,  are  not  so  abundant 
in  the  exudate.  It  is  a  fact  of  great  significance  that 
the  inflammatory  process  begins  simultaneously  in  the 
meninges  of  the  brain  and  cord.  WestenhoefFer  found 
the  earliest  evidence  of  inflammation  in  the  region 
of  the  hypophysis.  But,  as  Busse  points  out,  he 
failed  to  make  a  careful  microscopic  examination  of 
the  cord.  The  microscope  often  shows  a  purulent 
infiltration  in  areas  of  the  meninges  which  to  the 
naked  eye  appear  perfectly  normal.  As  we  shall  see 
later,  the  simultaneous  appearance  of  the  inflamma- 


88         MENINGOCOCCUS  MENINGITIS 

tion  in  the  brain  and  cord  speaks  strongly  for  a  blood 
invasion  of  the  meningococcus. 

The  ventricle  and  neighboring  brain  tissue  show 
microscopic  changes  in  all  cases.  The  ependymal 
lining  may  be  lost  in  parts  and  the  villi  of  the  choroid 
plexus  may  show  some  desquamation.  The  sup- 
ependymal  tissue  is  reticular  and  cedematous.  The 
blood-vessels  in  the  walls  of  the  ventricles  are  dilated 
and  surrounded  by  isolated  or  grouped  leucocytes. 
These  cells  tend  to  accumulate  about  that  part  of  the 
periphery  of  a  vessel  which  is  nearest  to  the  cavity 
of  the  ventricle.  The  villi  of  the  choroid  plexus  are 
congested  and  infiltrated  with  leucocytes. 

The  cortex  of  the  brain  is  reticular  and  cedema- 
tous. These  changes  are  particularly  marked  in  the 
cerebellum.  Isolated  leucocytes  are  present  in  the 
tissue  above  the  ganglion-cells.  At  times  they  are 
also  seen  in  the  white  substance  of  the  brain.  The 
blood-vessels  of  the  cortex  are  dilated.  Evidence  of 
some  perivascular  leucocytic  infiltration  is  present  in 
many  cases.  It  is  nevertheless  true  that  the  inflamma- 
tory process  is  largely  confined  to  the  meninges  and 
that  there  is  but  little  extension  to  the  parenchyma 
of  the  brain  and  cord.  Councilman,  Mallory  and 
Wright  describe  proliferation  of  the  neuroglia  and 
connective-tissue  cells  in  the  cortex  above  the  gang- 
lion-cells, beneath  the  ventricles,  and  particularly  in 


PATHOLOGIC  ANATOMY  89 

the    vicinity    of    foci    of    hemorrhage    and    cellular 
infiltration. 

Chronic  Stages. — With  advance  of  the  inflamma- 
tion the  greater  number  of  the  cells  in  the  exudate 
undergo  degeneration  and  fatty  metamorphosis.  The 
nuclei  lose  their  staining  power  and  are  later  con- 
verted into  granular  detritus.  The  large  cells  dis- 
appear. Lymphoid  and  plasma  cells  appear  in 
greater  numbers.  Organization  of  the  exudate  pro- 
ceeds by  the  formation  of  new  connective-tissue  cells 
and  capillaries.  The  yellow  opaque  areas  seen  by  the 
naked  eye  are  composed  of  cicatricial  tissue  contain- 
ing few  blood-vessels  and  cells.  In  the  ventricles  the 
organized  exudate  is  often  seen  to  be  connected  with 
the  tissue  beneath  the  ependyma.  The  walls  of  the 
ventricles  show  a  considerable  number  of  perivascular 
nodes  which  may  project  into  the  cavity  of  the  ventri- 
cle. They  are  largely  composed  of  lymphoid  cells. 
Suppuration  of  the  nodes  is  extremely  rare.  Busse 
has  observed  along  the  outer  border  of  the  cortex  of 
the  cerebellum  a  continuous  layer  of  cells  whose 
nuclei  are  placed  at  right  angles  to  the  circumference 
of  the  cerebellum  (palisade  cells).  These  are 
normally  seen  in  fetal  life  and  early  infancy.  Their 
presence  in  the  chronic  stages  of  meningitis  is  inter- 
preted by  him  as  a  reversal  to  fetal  structure. 


90         MENINGOCOCCUS  MENINGITIS 

In  subacute  and  chronic  cases  the  pyramidal  cells 
and  especially  the  cells  of  Purkinje  in  the  cerebellum 
show  evidence  of  degeneration  in  the  form  of  vacuo- 
lization and  chromatolysis. 

In  the  cord  Liebermeister  and  Lebsanft  have 
demonstrated  destruction  of  the  myelin  sheaths  and 
degeneration  of  the  fibres  in  the  peripheral  zones. 
This  process  was  especially  marked  in  the  more  pro- 
tracted cases.  The  ganglion-cells  of  the  anterior 
horns  give  evidence  of  degeneration.  Degeneration 
of  the  posterior  nerve-roots  occurs  in  the  protracted 
cases  as  a  result  of  the  purulent  infiltration  of  the 
arachnoid  which  ensheaths  the  roots.  The  cells  of 
the  spinal  ganglia  may  show  similar  degeneration. 

The  degeneration  of  the  nerve  tissue  proper  is  due 
to  imbibition  of  toxin.  Similar  changes  result  from  the 
action  of  other  micro-organisms  which  have  no  selec- 
tive affinity  for  the  nervous  system.  The  alterations, 
as  a  rule,  are  not  permanent. 

The  cranial  nerves  are  involved  as  a  result  of  the 
extension  of  the  inflammation  along  the  arachnoid 
which  envelops  them.  The  2d,  3d,  4th,  5th,  6th,  7th, 
and  8th  are  most  often  affected.  The  Gasserian 
ganglion  is  often  found  embedded  in  pus  at  an  early 
stage  of  the  disease.  The  purulent  exudate  may  ex- 
tend along  its  three  branches  to  the  orbit,  otic  gang- 


PATHOLOGIC  ANATOMY  91 

lion,  and  sphenopalatine  ganglion.  The  substance  of 
the  ganglion  does  not  undergo  suppuration.  In  pro- 
tracted cases  the  peripheral  nerves  may  show  de- 
generative changes. 

The  Meningococcus  in  the  Nervous  System. — The 
demonstration  of  the  meningococcus  in  the  acute 
stages  is  not  difficult,  providing  the  examination  is  not 
delayed.  In  the  exudate  the  meningococcus  is  often 
found  in  great  numbers,  both  within  and  without  the 
cells.  In  the  meninges,  especially  of  the  cord,  it  is 
less  abundant.  This  may  in  part  be  due  to  the  pro- 
cess of  hardening  of  the  tissues  which  may  exert  an 
injurious  action  on  the  staining  properties  of  the 
meningococcus.  In  the  chronic  cases  the  organism 
is  found  with  great  difficulty.  It  has  been  demon- 
strated in  areas  of  focal  softening  of  the  brain  and 
cord. 

The  Meningococcus  in  the  Blood. — The  meningo- 
coccus was  first  found  in  the  blood  by  Gwyn  in  a 
patient  of  Osier.  It  has  also  been  found  by  Cochez 
and  Lemaire,  Jakobitz,  Martini  and  Rohde,  Len- 
hartz,  Marcovitz,  Robinson,  Dieudonne,  Duval,  and 
others.  Elser  demonstrated  the  meningococcus  in  11 
out  of  41  cases.  In  a  number  of  cases  it  has  been 
found  in  patients  free  from  meningitis  (Salomon, 
Liebermeister,  Andrewes  and  Bovaird ) . 


92         MENINGOCOCCUS  MENINGITIS 

LESIONS  IN  OTHER  PARTS  OF  THE  BODY 

Upper  Respiratory  Tract. — -The  lesions  of  this 
tract  have  been  studied  with  minute  care  by  Westen- 
hoeffer.  He  found  marked  hyperemia,  slight  oedema, 
and  increased  secretion  of  the  adenoid  tissue  of  the 
nasopharynx  in  the  early  stages  of  the  disease,  due  to 
infiltration  of  lymphoid  and  plasma  cells.  The  nasal 
mucous  membrane  shows  similar  but  less  marked 
changes  in  adults.  In  children  inflammation  of  the 
nose  occurs  at  a  later  stage  as  a  complication.  The 
tonsils  are  much  less  often  affected.  The  mucous 
membrane  of  the  sphenoidal  sinus  and  the  antrum  of 
Highmore  are  somewhat  hyperaemic.  The  ethmoidal 
cells  show  still  less  change.  The  meningococcus  has 
never  been  found  either  in  the  bones  or  sinuses  of 
this  region. 

Lower  Respiratory  Tract. — Evidence  of  in- 
flammation of  the  bronchial  mucous  membrane  is  not 
infrequent  in  the  initial  stage  of  the  disease.  In 
fulminating  cases  passive  congestion  of  the  lungs, 
atelectasis,  foci  of  bronchopneumonia,  and  interstitial 
emphysema  may  be  present.  Pleurisy  with  serous, 
purulent,  or  sanguinolent  effusion  has  been  seen 
rather  frequently  in  some  epidemics. 

Lymph-nodes. — Inflammatory  swelling  of  the 
lymph-nodes  in  various  regions  of  the  body  is  common 


PATHOLOGIC  ANATOMY  93 

early  in  the  disease.  The  most  frequently  affected 
are  the  cervical,  submaxillary,  bronchial,  and  mesen- 
teric nodes.     Suppuration  never  occurs. 

Heart. — The  myocardium  may  show  inflamma- 
tory and  degenerative  lesions.  Westenhoeffer  de- 
scribes circumscribed  or  diffuse  infiltration  of  the 
cardiac  muscle,  also  cloudy  swelling  and  fatty  de- 
generation of  the  muscle-fibres.  In  a  number  of  cases 
these  changes  have  been  observed  before  the  onset 
of  meningeal  symptoms.  Evidence  of  fresh  valvulitis 
is  seen  occasionally  at  a  very  early  stage  of  the  disease. 
Meningococci  were  found  in  vegetations  by  Weichsel- 
baum  and  Ghon  and  Westenhoeffer.  In  the  cases  of 
Warfield  and  Walker  and  Cecil  and  Soper,  a  menin- 
gococcus endocarditis  was  present,  but  there  were  no 
evidences  of  meningitis.  Acute  serous  or  purulent 
pericarditis  has  been  seen  by  a  number  of  observers. 

G astro-intestinal  Tract. — In  the  mucous  mem- 
brane of  the  stomach  petechia?  may  be  present.  Occa- 
sionally hemorrhagic  erosions  are  seen,  due,  as  Busse 
thinks,  to  repeated  vomiting.  Petechia?  in  the  in- 
testinal mucosa  and  swelling  of  Peyer's  patches  and 
the  solitary  follicles  are  present  in  most  of  the  acute 
cases.  The  constancy  and  severity  of  these  lesions  in 
his  cases  led  Goeppert  to  express  the  opinion  that  the 
gastro-intestinal  tract  may  be  one  of  the  portals  of 
entry  of  the  meningococcus.   From  this  point  of  view 


94         MENINGOCOCCUS  MENINGITIS 

the  uniformly  negative  results  of  Councilman, 
Mallory  and  Wright  are  significant.  It  is  doubtful 
if  the  lesions  are  truly  inflammatory  in  nature.  Simi- 
lar changes  are  present  in  a  number  of  other  acute 
infectious  diseases.  Moreover,  Stuart  McDonald 
found  such  lesions  in  a  monkey  in  whom  meningitis 
was  produced  by  intradural  injection  of  cerebrospinal 
fluid  from  a  case  of  acute  meningitis.  It  is  not 
probable  that  the  meningococcus  can  pass  the  stomach 
containing  its  normal  degree  of  free  hydrochloric  acid 
with  its  pathogenic  powers  undiminished. 

Liver. — In  most  cases  there  is  no  evidence  of  in- 
flammation in  this  organ.  The  interstitial  changes 
found  by  Bettencourt  and  Franca  may  have  had  no 
connection  with  the  disease. 

Spleen. — As  a  rule,  there  is  no  enlargement  of  this 
organ.  The  pulp  may  be  more  vascular.  The  Mal- 
pighian  corpuscles  at  times  show  some  degree  of 
enlargement. 

Kidneys. — There  are  no  constant  changes  in  the 
kidneys.  The  most  frequent  lesion  is  an  acute  de- 
generation of  the  kidney,  shown  by  cloudy  swelling 
and  fatty  degeneration  of  the  epithelial  lining  of  the 
tubules. 

Inflammatory  changes  in  the  bladder,  seminal 
tract,  and  urethra  are  rare.    Pick  observed  a  case  of 


PATHOLOGIC  ANATOMY  95 

double  empyema  of  the  seminal  vesicles  in  which  the 
meningococcus  was  readily  demonstrable. 

Joints. — In  most  of  the  cases  in  which  symptoms 
referable  to  the  joints  are  seen  during  life,  there  are 
few  post-mortem  changes.  Suppuration  is  very  rare. 
Neither  Westenhoeff  er  nor  Btisse  met  with  a  case  of 
arthritis  at  post-mortem.  The  meningococcus,  unlike 
the  gonococcus,  almost  never  produces  changes  in  the 
periarticular  structures. 

Skin. — In  the  purpuric  lesions  the  vessels  are 
dilated;  there  are  small  hemorrhages  and  leucocytic 
infiltration  beneath  the  epithelium.  Meningococci 
have  been  found  in  the  herpetic  lesions  by  v.  Drigalski 
and  Herford. 

Bibliography 

Klebs:     Virch.  Archiv,  1865,  xxxiv,  327. 

Flexner   and   Barker:      Amer.    Jour.    Med.    Sciences,    1894, 

cvii,  155. 
Councilman,  Mallory  and  Wright:     Report  State  Board  of 

Health  of  Mass.,  Boston,  1898. 
Gwyn :    Bull.  Johns  Hopkins  Hosp.,  1899,  x,  112. 
Bettencourt  and  Franca:     Zeit.   f.   Hyg.   u.   Infect.,   1904, 

xlvi,  463. 
v.  Drigalski:    Deut.  med.  Wochenschr.,  1905,  xxi,  982. 
Westenhoeffer :    Klin.  Jahrbuch,  1906,  xv,  447. 
Peters:     Deutsche  med.  Wochenschr.,  1906,  xxxii,  1151. 
Pick:     Berl.  klin.  Wochenschr.,  1907,  xliv,  947. 
McDonald:    Jour.  Path,  and  Bact.,  1908,  xii,  442. 


96         MENINGOCOCCUS  MENINGITIS 

Herford:     Klin.  Jahrbuch,  1908,  xix,  265. 

Liebermeister   and   Lebsanft:      Muench.   med.   Wochenschr., 

1909,  lvi,  914. 
Goeppert:     Ergebnisse  d.  Innere  Med.  u.  Kinderhk.,  1909, 

iv,  165. 
Bovaird:    Arch.  Int.  Med.,  1909,  iii,  267. 
Busse:    Klin.  Jahrbuch,  1910,  xxiii,  363. 
Cecil  and  Soper:    Arch.  Int.  Med.,  1911,  vlii,  1. 
Striimpell:     Lehrbuch  d.   spec.   Path.   u.   Therap.,  Leipzig, 

1912,  18  Aufl. 


CHAPTER  VI 

Clinical  Types  of  Meningococcus  Meningitis 

It  is  not  surprising  that  there  is  lack  of  uniformity 
among  writers  as  regards  the  classification  of  this 
form  of  meningitis.  Properly  speaking,  a  typical 
course  of  meningococcus  meningitis  does  not  exist. 
The  irregular  features  of  its  epidemiology  are  seen 
once  more  in  its  symptomatology.  Strict  adherence 
to  accuracy  would  limit  our  clinical  description  of  the 
disease  to  an  enumeration  and  discussion  of  a  multi- 
tude of  individual  symptoms  and  signs.  However, 
to  obviate  the  vagueness  of  such  a  mode  of  treatment 
we  must  forego  strict  accuracy  and  describe  a  number 
of  types.  We  may  therefore  classify  the  disease  as 
follows : 

„     _    ,.  f  Acute  stage. 

1.  Ordinary \  .      & 

(  Chronic  stage. 

,  ,.  (  Fulminating. 

2.  Malignant ]  & 

(  Hyperacute. 

!3.   Mild. 

4.  Abortive. 

5.  Intermittent. 

6.  Posterior-basic. 

Ordinary  Type. — This  is  the  usual  form  of  mani- 
festation of  the  disease  in  the  adult  and  older  child. 

7  97 


98         MENINGOCOCCUS  MENINGITIS 

It  occurs  sporadically  and  in  epidemics.  The  dura- 
tion of  the  incubation  period  is  from  three  to  five 
days.  The  onset  is  usually  abrupt  and  violent.  Ex- 
ceptionally, the  onset  is  preceded  by  a  short  period  of 
general  malaise,  nausea,  loss  of  appetite,  headache 
and  pains  in  the  back,  coryza  and  sore  throat.  More 
commonly,  however,  the  patient  is  attacked  in  the 
midst  of  perfect  health  by  a  sudden  chill,  rapid  rise 
of  temperature,  severe  headache,  and  repeated  vomit- 
ing. In  childhood  the  chill  is  not  uncommonly  re- 
placed by  one  or  more  convulsions.  The  symptoms 
of  invasion,  as  can  be  seen,  are  in  no  way  characteris- 
tic. They  are  not  unlike  those  seen  at  the  onset  of  a 
number  of  other  acute  infectious  diseases,  such  as 
pneumonia  and  scarlet  fever. 

After  a  short  period,  varying  usually  from  twelve 
to  forty-eight  hours,  during  which  a  remission  of  the 
symptoms  seen  at  the  onset  may  occur,  the  phenomena 
characteristic  of  meningeal  involvement  appear.  It 
is  purely  dogmatic,  and  not  in  accord  with  the  clinical 
picture,  to  speak  of  successive  stages  of  excitation 
and  depression  at  this  period  of  the  disease. 

The  earliest  truly  characteristic  symptoms  are 
stiffness  of  the  head  and  neck,  reflected  pains  in  the 
head,  neck,  and  limbs,  and  hyperesthesia  along  the 
back  of  the  head  and  spine.  There  appears  simultan- 
eously a  contracture  of  the  hamstring  muscles  of  the 


CLINICAL  TYPES  99 

legs,  known  as  the  Kernig  sign,  which  is  present  in 
almost  all  forms  of  meningitis.  With  the  develop- 
ment of  the  disease  the  neck  rigidity  becomes  more 
marked ;  retraction  of  the  head  and  more  or  less  ortho- 
tonus appear.  The  head  becomes  immobile,  permit- 
ting neither  lateral  nor  anteroposterior  movement 
without  great  pain.  When  an  attempt  is  made  to 
flex  the  head  on  the  chest  by  lifting  it  from  the  pillow, 
the  whole  trunk  is  raised.  The  spine  is  rigid,  as 
though  composed  of  one  bone.  The  headache,  due  to 
increased  intracranial  pressure  and  compression  of  the 
nerve-trunk,  usually  persists  throughout  the  whole 
course  of  the  disease.  It  is  chiefly  localized  in  the 
back  of  the  head.  Hyperesthesia  is  pronounced.  The 
slightest  touch,  especially  of  the  neck  and  spine,  pro- 
duces agonizing  pain,  and  in  children  may  elicit 
piercing  cries.  The  patients  are  very  sensitive  to  light 
and  sound.  In  children  a  coarse  intention  tremor  is 
often  present  at  an  early  stage  of  the  disease.  Confu- 
sion and  quiet  delirium  occur  frequently ;  unconscious- 
ness is  rare.  Wakefulness  is  a  common  symptom. 
There  are  frequent  periods  of  restlessness,  during 
which  the  patient  tosses  from  one  side  of  the  bed  to 
the  other.  The  face  is  alternately  pale  and  flushed, 
indicating  the  instability  of  the  vasomotor  apparatus. 
The  pupils  are  usually  equal  and  react  sluggishly  to 
light.    Attempted  flexion  of  the  head  produces  transi- 


100       MENINGOCOCCUS  MENINGITIS 

tory  dilatation.  Alternate  contraction  and  dilatation 
of  the  pupils  is  often  present  (hippus).  Transitory 
strabismus  is  occasional^  seen,  but  is  much  less  fre- 
quent than  in  tuberculous  meningitis.  The  tongue  is 
dry  and  coated.  The  patients  usually  lie  on  the  side 
with  the  legs  flexed  at  the  hip  and  knees.  After  the 
third  day  a  number  of  herpetic  vesicles  usually  appear 
on  the  face  about  the  lips  and  nose.  In  some  epi- 
demics a  considerable  number  of  patients  show  a  pro- 
fuse petechial  or  purpuric  eruption  at  an  early  stage 
of  the  disease.  The  temperature  is  variable  and  not 
characteristic.  It  is  often  marked  by  great  irregu- 
larity and  wide  fluctuations  within  short  periods  of 
time.  The  pulse  shows  considerable  variations  in  rate 
and  character.  Bradycardia  is  much  less  frequent 
than  in  tuberculous  meningitis.  The  respirations  are 
rapid,  but  not  out  of  proportion  to  the  temperature. 
There  is  usually  present  a  well-marked  tache  cere- 
brale  characterized  by  early  appearance,  intensity,  and 
persistence.  The  bowels  are  usually  constipated. 
Goeppert,  however,  has  seen  a  large  number  of  cases 
in  which  diarrhoea  was  a  persistent  symptom.  In  a 
variable  number  of  cases,  acute  suppurative  otitis 
media  develops.  Spontaneous  rupture  of  the  drum 
membrane  is  extremely  rare.  The  spleen  is  occasion- 
ally somewhat  enlarged.  The  urine  is  often  increased 
in  quantity.    At  times  it  may  contain  albumin,  but 


CLINICAL  TYPES  101 

rarely  any  other  evidences  of  nephritis.  Involvement 
of  the  joints  is  frequent  in  some  epidemics,  very  rare 
in  others. 

The  duration  and  course  of  the  disease  are  very 
variable.  It  may  terminate  in  death,  recovery,  or  the 
chronic  stage  of  the  disease.  More  than  fifty  per  cent, 
of  the  fatal  cases  die  within  the  first  week.  In  these 
cases  the  rigidity  and  Kernig  sign  remain  unabated  or 
become  aggravated.  Great  prostration  develops,  with 
extremely  rapid  irregular  pulse  and  labored  respira- 
tion, which  is  often  of  the  Cheyne-Stokes  type.  The 
delirium  passes  into  stupor  and  coma.  Before  death 
general  relaxation  sets  in,  and  the  temperature  may 
rise  rapidly  to  105°  or  106°  F.  In  other  cases  sudden 
collapse  and  rapid  fall  of  temperature  may  occur,  and 
death  takes  place  unexpectedly  within  a  few  hours. 

Beginning  recovery  is  usually  presaged  by  reduc- 
tion of  the  temperature  and  diminution  of  the  head- 
ache, pains  in  the  back,  hyperesthesia,  restlessness, 
and  rigidity  of  the  neck  and  limbs.  The  Kernig  sign 
persists  for  some  time  after  all  the  other  symptoms 
have  disappeared.  Recovery  usually  takes  place 
within  from  ten  to  thirty  days.  At  any  time  within 
this  period  sudden  exacerbation  of  the  characteristic 
symptoms  may  set  in.  In  most  of  the  cases  convales- 
cence is  uninterrupted  and  complete. 

In  a  variable  number  of  cases  the  acute  stage 


102       MENINGOCOCCUS  MENINGITIS 

passes  gradually  and  imperceptibly  into  the  chronic 
stage,  which  may  last  from  two  to  six  months  or 
longer.  Progressive  emaciation  appears,  due  most 
probably  to  trophic  disturbances.  The  temperature 
varies  markedly.  For  longer  or  shorter  periods  it 
may  be  normal  or  even  subnormal.  Sudden,  irregular 
accessions  of  fever  may  occur  from  time  to  time.  The 
mind  may  remain  clear  to  the  end.  In  other  cases 
mental  weakness  develops.  Adults  may  become 
childish  and  children  show  no  interest  in  anything  but 
food.  Rigidity  of  the  neck  and  spine  and  the  Kernig 
sign  persist  through  the  chronic  stage.  Active  move- 
ments of  the  limbs  become  awkward  and  are  often 
accompanied  by  well-marked  tremor.  At  times  there 
may  be  paroxysms  of  tremor  of  the  arms  and  legs 
following  excitement  or  unusual  effort.  Even  in 
adults  there  are  often  in  this  stage  incontinence  and 
retention  of  urine  and  fseces.  Due  to  this  and  the 
trophic  disturbances  mentioned  above,  bed-sores  often 
make  their  appearance.  The  most  common  complica- 
tion of  this  stage  is  chronic  hydrocephalus,  the  symp- 
toms of  which  will  be  described  in  another  section. 
Most  of  the  cases  finally  succumb  to  marasmus. 
Death  is  often  preceded  by  one  or  more  convulsions. 
However,  even  in  the  apparently  hopeless  cases  re- 
covery is  possible.  Gradually  the  rigidity  becomes 
less  marked,  the  febrile  attacks  less  frequent,  the  mind 


CLINICAL  TYPES  103 

more  active.  Convalescence  is  extremely  tedious,  the 
neck  is  very  weak  and  unable  to  support  the  head 
fully,  and  the  gait  is  awkward  for  a  considerable  time. 
The  mental  power  in  most  of  the  cases  that  recover 
returns  in  full  vigor.  The  changes  in  the  cerebro- 
spinal fluid  will  be  described  in  another  chapter. 

Fulminating  Type. — These  cases  are  usually  seen 
in  the  early  periods  of  an  epidemic.  They  are  char- 
acterized by  intensity  of  the  onset  and  rapidity  of  the 
course.  The  disease  may  begin  with  violent  head- 
ache, vertigo,  convulsive  seizure,  and  high  fever.  In 
other  cases  the  onset  differs  in  no  wise  from  an 
apoplectic  attack,  the  patient  passing  rapidly  into 
deep  coma.  There  is  extreme  prostration,  with  irregu- 
lar thready  pulse,  labored  irregular  respirations, 
often  Cheyne-Stokes  in  character,  and  coldness  and 
cyanosis  of  the  extremities.  A  petechial  or  purpuric 
eruption  on  the  chest,  abdomen,  or  extremities 
appears.  The  fatal  termination  usually  occurs  within 
from  ten  to  thirty  hours  after  the  onset,  often  before 
the  characteristic  symptom  of  rigidity  has  had  time 
to  develop. 

Hyperacute. — These  cases,  many  of  which  are 
seen  at  the  height  of  an  epidemic,  resemble  the  ordi- 
nary form,  but  the  symptoms  are  more  marked  and 
rapid  in  their  development.  The  temperature  is 
usually  very  high,  the  rigidity  of  the  neck  and  spine 


104       MENINGOCOCCUS  MENINGITIS 

extreme,  and  the  Kernig  sign  pronounced.  There  is 
marked  delirium  and  restlessness.  The  pulse  is  rapid 
and  weak,  the  respiration  labored,  and  the  extremities 
are  cold  and  cyanotic.  A  petechial  or  purpuric  erup- 
tion is  often  present,  and  metastatic  foci  of  suppura- 
tion are  not  uncommon. 

Mild  Type. — These  cases  are  not  infrequent  in  the 
declining  stage  of  an  epidemic.  This  type  of  the 
disease  may  attack  a  large  number  of  individuals  in 
a  school,  regiment,  or  village.  The  onset  is  much  less 
abrupt.  The  patients  complain  of  general  malaise, 
anorexia,  moderate  headache,  and  pains  in  the  spine 
and  limbs.  The  temperature  may  not  rise  above 
101°  F.  The  rigidity  of  the  neck  is  not  very  pro- 
nounced. At  times  it  simulates  an  ordinary  torti- 
collis. The  disease  usually  runs  its  course  within  a 
week.  Convalescence  is  rapidly  established.  At 
times  the  subjective  symptoms  are  so  slight  that  the 
patient  is  able  to  pursue  his  work  with  practically  no 
interruption  ( ambulatory  cases ) . 

Abortive  Type. — The  onset  and  early  course  of 
the  disease  differ  in  no  wise  from  those  seen  in  the 
ordinary  type  of  the  disease.  At  the  end  of  two  to 
five  days,  however,  there  is  sudden  cessation  of  all 
symptoms  and  convalescence  is  established.  Some  of 
the  cases  are  marked  by  a  number  of  short  relapses. 

Intermittent  Type. — The  fever  curve  resembles 


CLINICAL  TYPES  105 

closely  the  type  seen  in  tertian  malaria.  The 
paroxysms,  however,  are  of  longer  duration  and  they 
do  not  show  the  regularity  as  to  time  of  occurrence 
which  is  such  a  marked  feature  of  malaria.  The 
meningeal  symptoms  vary  in  severity,  but  usually  run 
parallel  with  the  temperature  curve.  The  mildness 
of  the  characteristic  symptoms  of  meningeal  involve- 
ment has  often  led  to  the  mistaken  diagnosis  of 
malaria.    The  course  is  usually  protracted. 


CHAPTER  VII 

Meningococcus  Meningitis  in  Infancy 

Up  to  within  a  comparatively  recent  period,  the 
opinion  was  quite  general  that  this  affection,  espe- 
cially that  form  which  occurs  sporadically,  was  rare  in 
infancy.  This  is  in  large  part  due  to  the  fact  that, 
previous  to  the  general  adoption  of  lumbar  puncture 
as  a  diagnostic  aid,  the  disease  was  frequently  not 
recognized.  The  difficulties  encountered  in  the  diag- 
nosis, the  high  mortality,  and  the  frequent  occurrence 
of  serious  complications  and  sequelae  demand  a  some- 
what extended  treatment  of  the  infantile  forms  of 
meningococcus  meningitis. 

Fulminating  cases  occur  in  the  infant  as  well  as  in 
the  adult,  but,  probably  on  account  of  lack  of  char- 
acteristic symptoms,  more  often  escape  recognition. 

The  usual  type  begins  abruptly  in  the  infant  al- 
most as  often  as  in  the  adult.  At  least  in  the  great 
majority  of  our  own  cases  there  was  a  definite  history 
of  sudden  onset.  It  must,  however,  be  admitted  that 
the  French  authors,  such  as  Netter  and  Debre,  speak 
of  an  insidious  onset,  with  slight  fever,  listlessness, 
somnolence,  vomiting,  and  diarrhoea,  as  the  one  most 
common  at  this  age.  Rapid  rise  of  temperature, 
vomiting,  and  convulsions  were  present  at  the  onset 

106 


MENINGITIS  IN  INFANCY  107 

of  many  of  our  cases.  With  the  development  of  the 
disease,  three  important  symptoms  make  their  appear- 
ance,— namely,  hyperesthesia,  rigidity  of  the  neck, 
and  bulging  anterior  fontanelle.  The  hyperesthesia 
is  at  times  the  one  prominent  symptom.  In  a  number 
of  cases  Goeppert  was  enabled  to  make  an  early 
diagnosis  by  this  symptom  alone.  The  presence  of 
hyperesthesia  is,  according  to  this  author,  best  demon- 
strated by  moving  the  legs  or  attempting  to  sit  up 
the  patient.  The  rigidity  of  the  neck,  though  usually 
present,  is  occasionally  so  slight  that  it  must  be  sought 
for  in  a  most  painstaking  manner.  To  detect  the 
slightest  degrees  of  rigidity,  Xetter  and  Debre  advise 
that,  at  the  end  of  a  thorough  physical  examination, 
the  baby  should  be  placed  naked  on  a  flat  table,  when 
the  slighest  retraction  of  the  head  or  rigidity  of  the 
spine  becomes  more  pronounced,  as  a  result  of  the 
previous  manipulation  of  the  patient. 

Tension  and  bulging  of  the  anterior  fontanelle  is 
an  important  symptom  and  should  always  be  sought 
for  in  febrile  babies.  Its  presence  is  of  especial 
significance  in  infants  suffering  from  watery  diar- 
rhoea, in  whom  the  fontanelle  is,  as  a  rule,  depressed. 
Another  symptom  of  meningeal  involvement,  which  in 
our  experience  is  constantly  present  at  this  age,  is  the 
loss  of  ability  to  sit  up  in  bed.  We  have  also  found 
a  well-marked  tremulousness  of  the  hands  on  active 


108       MENINGOCOCCUS  MENINGITIS 

motion  a  frequent  symptom  throughout  the  course  of 
the  disease.  The  Macewen  sign,  indicative  of  in- 
creased fluid  in  the  cerebral  ventricles,  becomes  of 
value  only  after  the  fontanelle  is  closed.  The  Kernig 
sign  is  practically  devoid  of  diagnostic  value  below 
two  years  of  age.  Restlessness  may  be  present; 
usually,  however,  the  infants  are  somnolent  and  quiet 
unless  disturbed,  when  they  emit  piercing  cries  of 
pain.  Even  more  frequently  than  in  adults  and  older 
children  does  this  form  of  meningitis  in  infants  ter- 
minate in  death  or  in  a  protracted  chronic  stage. 

Typical  Case. — C.  S.,  age  5  months ;  admitted  May  26, 
1903;  discharged  cured  July  9,  1903: 

Family  and  Past  History. — Negative. 

Present  History. — Sudden  onset  five  weeks  ago,  with 
general  convulsion  and  high  fever  (which  lasted  three  weeks). 
Child  vomits  two  or  three  times  a  day ;  pro j  ectile  in  character. 
Child  sleeps  much,  but  is  irritable.  Head  retracted  since 
onset;  bowels  constipated.  Child  has  emaciated.  Three  days 
ago  convulsions  recurred,  and  there  have  been  two  per  day 
since  then. 

Examination. — Child  lies  quietly  in  bed;  legs  drawn  up; 
cries  when  disturbed.  General  condition  poor.  Eyes  turned 
downward,  otherwise  normal.  Anterior  fontanelle  wide  open. 
Head  large  and  square.  Marked  opisthotonus,  rigidity  of 
neck,  and  general  hyperesthesia.  Kernig  present;  marked 
tache  cerebrale.  Entire  right  upper  extremity  held  flexed, 
but  there  is  no  rigidity  or  palsy  of  any  limb.  Heart  action 
irregular,  rapid.     Abdomen  slightly  retracted. 


MENINGITIS  IN  INFANCY  109 

Clinical  Notes. — May  27 :  Leucocytes  12,000.  Lumbar 
puncture:  45  cubic  centimetres  fairly  clear  fluid  obtained. 
Contains  meningococci  in  spreads  and  cultures.  Immediately 
after  puncture  eyes  were  no  longer  rolled  down,  but  were  held 
in  normal  position. 

May  28:    Leucocytes  22,000.     Fontanelle  bulging. 

May  31 :  Two  days  ago  temperature  came  down  and  has 
remained  normal.  Apathy  continues.  Eyes  again  rolled 
down.  Opisthotonus  marked ;  hyperaesthesia  continued. 
Another  lumbar  puncture  done. 

June  3:  Fontanelle  again  bulging;  eyes  rolled  down. 
Chvostek  present.  Temperature  remains  normal.  No 
vomiting. 

June  6 :  Temperature  normal  for  past  week.  Fontanelle 
bulging.     General  condition  practically  unchanged. 

June  8:  Third  lumbar  puncture:  12  cubic  centimetres 
removed. 

June  9 :  Temperature  remains  normal.  Child  seems 
brighter.  No  more  opisthotonus.  Slight  hyperesthesia  and 
slight  rigidity  of  neck  still  present. 

June  12:  Child  brighter.  Fontanelle  soft.  Eyes  not 
rolled  down.  Abdomen  retracted.  No  hyperesthesia.  Neck 
very  rigid. 

June  15:  Fourth  lumbar  puncture:  25  cubic  centimetres 
withdrawn  under  pressure. 

June  18:  Temperature  normal;  pulse  regular.  Abdomen 
retracted.  Opisthotonus  and  neck  rigidity  still  present.  No 
hyperesthesia. 

June  21 :  Child  gaining  in  weight.  Seems  brighter.  No 
more  opisthotonus.  Rigidity  of  neck  disappearing.  Leuco- 
cytes 13,000. 


110       MENINGOCOCCUS  MENINGITIS 

July  3 :   Fontanelle  slightly  depressed. 

July  9:  Fontanelle  no  longer  depressed.  Temperature 
normal.  Child  has  gained  weight.  No  meningitis  symptoms. 
Discharged  cured. 

Posterior  Basic  Meningitis. — This  form  of  menin- 
gitis, seen  almost  exclusively  in  the  first  two  years  of 
life,  was  first  described  by  Gee  and  Barlow  in  1878 
under  the  name  of  "  cervical  opisthotonus  of  infants." 
Their  observations  were  based  on  twenty-five  sporadic 
cases,  some  of  which  had  a  sudden,  others  a  gradual 
onset.  The  most  striking  feature  was  a  "  holding 
back  of  the  head."  Other  characteristic  symptoms 
were  fever,  vomiting,  convulsions,  and  rigidity  of  the 
limbs.  At  autopsy  a  variable  amount  of  purulent 
exudate  at  the  base  and  dilatation  of  the  ventricles 
were  found.  In  1897  Carr  again  described  a  number 
of  cases,  and  attributed  the  hydrocephalus  which  is  a 
frequent  complication  to  two  causes, — namely  (1) 
obliteration  of  the  foramen  of  Magendie,  thus  pre- 
venting the  escape  of  cerebrospinal  fluid  from  the 
ventricles;  (2)  compression  of  the  basilar  vessels  by 
exudate,  sometimes  causing  a  thrombosis  of  the  veins 
of  Galen,  thus  producing  a  passive  hyperemia  and 
transudation  of  serum  in  the  ventricles.  In  1898 
Still  gave  an  admirable  clinical  description  of  this 
type  of  meningitis.  In  seven  out  of  eight  cases  he 
succeeded  in  finding  in  the  exudate  of  the  ventricles 


PLATE  IV 


Posterior  l>  isic  meningitis,  child  -i\  months  "I  age.     '  Koplik.  | 


Fig.  10. — Posterior  basic  meningitis,  age  eleven  months. 


MENINGITIS  IN  INFANCY  111 

and  subarachnoid  space  a  diplococcus  which  closely 
resembled  the  dij3lococcus  of  Weichselbaum.  It 
apparently  differed  from  the  meningococcus  in  grow- 
ing more  readily  on  plain  agar  and  in  broth.  On 
agar  it  could  be  kept  alive  for  twenty-four  to  thirty- 
four  days;  on  blood  agar  for  fifty-three  days.  It 
possessed  very  feeble  pathogenic  properties  for 
laboratory  animals.  Despite  these  differences,  Still 
expressed  the  opinion  that  the  germ  discovered  by 
him  was  merely  a  variety  of  the  meningococcus  and 
not  a  distinct  species.  In  1905  Koplik  first  estab- 
lished the  important  fact  that  posterior  basic  menin- 
gitis may  occur  in  epidemic  as  well  as  in  sporadic 
form.  Among  thirty  of  his  cases  of  epidemic  menin- 
gococcus meningitis  there  were  eight  cases  of  the 
posterior  basic  type. 

Pathologic  Anatomy  (Plate  IV). — The  patho- 
logic anatomy  of  this  type  differs  from  that  of  the 
ordinary  adult  type  in  that  the  primary  seat  of  the 
inflammation  is  at  the  posterior  part  of  the  base  of 
the  brain, — i.e.,  where  the  medulla  passes  into  the 
spinal  cord.  A  yellow  fibrino-purulent  exudate  fills 
up  the  cisterna  magna.  From  this  region  it  spreads 
downward  for  a  variable  distance  along  the  posterior 
aspect  of  the  cord,  inward  toward  the  ventricles,  and 
forward  along  the  base  of  the  brain  as  far  as  the 


112       MENINGOCOCCUS  MENINGITIS 

interpeduncular  space,  the  optic  chiasm,  and  the  tips 
of  the  tempero-sphenoidal  lobes.  It  is  often  stated 
that  the  vertex  is  rarely  involved.  Langmead,  how- 
ever, states  that  in  19  out  of  50,  or  about  40  per  cent, 
of  the  autopsies  at  the  London  Sick  Hospital  for 
Children,  the  inflammation  was  demonstrable  at  the 
vertex,  but  was  never  primary  there.  The  ventricles 
are  almost  always  dilated  and  filled  with  clear  or 
turbid  fluid. 

Clinical  Course  (Fig.  10).— The  disease  belongs 
pre-eminently  to  early  infancy.  It  is  seldom  seen  in 
children  above  two  years  of  age.  The  youngest 
patient  of  our  series  was  four  months  old,  the  oldest 
five  years.  The  onset  is  usually  sudden,  with  fever, 
vomiting,  and  at  times  a  convulsion.  After  the  lapse 
of  several  hours  or  days  the  characteristic  retraction 
of  the  head  sets  in.  This  feature  is  so  striking  that  a 
diagnosis  of  the  condition  can  be  made  at  a  glance. 
With  the  retraction  there  is  associated  more  or  less 
opisthotonus.  The  arching  of  the  back  is  at  times  so 
pronounced  that  the  head  may  touch  the  sacrum.  The 
chest  shows  marked  anterior  bulging,  while  the  abdo- 
men is  rigid  and  retracted.  The  position  of  the  ex- 
tremities varies.  Most  often  they  are  found  in  rigid 
extension.  The  hands  are  pronated  and  the  fists 
clenched,  giving  the  driving  position  characteristic 


MENINGITIS  IN  INFANCY  113 

of  tetany.  The  legs  are  adducted,  at  times  crossed. 
The  foot  may  show  extreme  extension  at  the  ankle. 
In  other  cases  there  is  flexion  of  the  limbs  at  the 
various  joints.  But  whether  in  extension  or  flexion 
the  spasticity  of  the  limbs  is  such  that  it  can  not  be 
overcome  by  permissible  efforts  on  the  part  of  the 
physician.  From  time  to  time  relaxation  may  occur. 
The  slightest  disturbance,  however,  causes  immediate 
reappearance  of  the  spasticity. 

The  open  fontanelles  are  tense  and  bulging,  and 
in  the  younger  infants  there  is  often  wide  separation 
of  the  sutures  and  dilatation  of  the  veins  of  the  scalp. 
This  is  due  to  progressive  increase  of  fluid  in  the 
ventricles.  The  pupils  are  usually  dilated  and  the 
upper  lids  retracted.  The  resulting  exposure  of  the 
upper  part  of  the  sclera  gives  the  patients  a  peculiar 
blank  staring  look.  Strabismus  is  usually  present 
in  the  later  stages  of  the  disease.  About  one-third 
of  the  patients  exhibit  some  degree  of  blindness.  This 
symptom  is  of  central  origin,  as  in  most  of  the  cases 
the  disks  are  quite  normal. 

The  patients  are  apathetic  and  lie  quietly  for  hours 
at  a  time  without  a  movement  or  sound.  Food  is 
devoured  greedily.  Vomiting  is  often  a  very  trouble- 
some symptom.  It  may  occur  paroxysmally  through- 
out the  course  of  the  disease.     It  is  often  projectile 

8 


114       MENINGOCOCCUS  MENINGITIS 

in  character.  The  temperature  varies  markedly.  At 
the  onset  it  may  range  from  101°  to  103°  F.  for 
several  days  or  a  week.  At  a  later  stage  it  may  be 
normal  or  only  slightly  above  normal.  From  time  to 
time  the  temperature  may  show  wide  excursions. 
Immediately  preceding  death  hyperpyrexia  may 
appear. 

Progressive  emaciation  is  a  feature  equally  as 
constant  as  the  retraction  of  the  head.  The  patients 
often  become  worn  to  a  skeleton.  The  vasomotor 
paresis  is  evidenced  by  the  presence  of  tache  cere- 
brale  and  transitory  erythemas.  The  Kernig  sign 
is  difficult  to  obtain  because  of  the  rigidity.  The 
Babinski  reflex  is  rarely  present.  There  is  usually  a 
slight  leucocytosis.  It  is  rarely  above  25,000  to  the 
cubic  millimetre.  In  this  respect  the  disease  re- 
sembles  tuberculous  meningitis. 

Dry  taps  on  lumbar  puncture  are  comparatively 
frequent.  This  is  attributable  either  to  obliteration 
of  the  foramen  of  Magendie  or  to  adhesions  at  the 
base  of  the  brain  shutting  off  the  cranial  ventricles 
and  subarachnoid  space  from  the  spinal  canal. 
In  those  cases  in  which  a  sufficient  amount 
of  cerebrospinal  fluid  is  obtained,  it  is  not  infre- 
quently sterile.  The  ventricular  fluid  on  puncture 
or    at    autopsy    occasionally    shows    the    meningo- 


MENINGITIS  IN  INFANCY  115 

coccus  in  cases  where  the  fluid  obtained  by  lumbar 
puncture  had  previously  given  a  negative  bacterio- 
logic  result. 

Identity  of  Posterior  Basic  Meningitis  with 
Meningococcus  Meningitis. — The  distinctive  clinical, 
bacteriological,  and  pathological  features  of  this  type 
of  meningitis  have  led  a  number  of  British  clinicians 
to  assume  that  posterior  basic  meningitis  is  a  disease 
per  se.  There  can  be  little  doubt  at  the  present  time, 
however,  that  it  is  merely  a  variety  of  meningococcus 
meningitis. 

Hunter  and  Nuttall  in  seven  typical  cases  re- 
covered organisms  from  the  cerebrospinal  fluid 
obtained  by  lumbar  puncture  which  were  absolutely 
identical  with  the  diplococcus  described  by  Weichsel- 
baum.  Dopter  and  Martha  Wollstein  have  shown 
identical  agglutination  reactions  of  the  two  organ- 
isms. Moreover,  Langmead  has  demonstrated  the 
similarity  in  the  pathologic  anatomy  of  the  two  dis- 
eases by  showing  involvement  of  the  vertex  of  the 
brain  in  19  and  exudate  in  the  ventricles  in  34  out 
of  50  cases  of  posterior  basic  meningitis.  The  diiFer- 
ences  in  the  clinical  picture,  the  absence  of  herpes  and 
rashes,  and  the  presence  of  amaurosis  are  probably 
attributable  to  age.  Langmead  has  shown  that  in 
children  over  SV-j  years  of  age,  posterior  basic  menin- 
gitis runs  a  course  very  similar  to  the  ordinary  type 


116       MENINGOCOCCUS  MENINGITIS 


of  meningococcus  meningitis,  as  is  shown  in  the  fol- 
lowing table: 


Rash. 


Temperature. 


Optic 
neuritis. 


Amaurosis. 


Posterior  basic  men- 
ingitis in  infanta 


Posterior  basic  men- 
ingitis in  older 
children 

Cerebrospinal  fever 


Very  rarely 


2  in  10  her- 
pes 


6  in  30  pur- 
puric, 5  in 
30  herpes, 
New  York 
epidemic 


Usually  slight; 
higher  and  ir- 
regular if  fatal 

8  in  10  irregu- 
larly intermit- 
tent 

No  fixed  type, 
but  one  form 
intermittent 


per  cent. 

3  in  42  =  7 

(Barlow 

and  Lees) 

5  in  10  =  50 


6  in  40  =  15 
(Randolph) 


At  least 


1  in  10. 


Very 
rarely. 


We  are  therefore  justified  in  assuming  that 
posterior  basic  meningitis  is  a  form  of  meningococcus 
meningitis  seen  in  a  certain  number  of  infants  and 
young  children. 

Bibliography 

(Chapters  Viand  VII  ) 

Stille :    Epidemic  Meningitis,  Phila.,  1867. 

Gee  and  Barlow:     St.  Bartholomew's  Hosp.  Reports,  1878, 

xiv,  23. 
Carr:     Medico-Chirurg.  Transactions,  1897,  lxxx,  303. 
Still:     Transactions  Path.  Soc.  of  London,  1898,  xlix,  313. 
Koplik:     Amer.  Jour.  Med.  Sciences,  1905,  cxxix,  266. 
Langmead:    Practitioner,  1907,  v,  485. 
Wollstein:    Jour.  Exp.  Med.,  1907,  ix,  588. 
Goeppert :    Ergeb.  d.  Inner  Med.,  Kinderhk.,  1909,  iv,  165. 
Netter  and  Debre:  La  Meningite  Cerebrospinale,  Paris,  1911. 


CHAPTER  VIII 

Symptomatology 

Pathogenesis. — In  the  causation  of  the  multiplicity 
of  symptoms  of  the  disease  several  factors  are  in- 
volved: First,  the  local  growth  of  the  meningo- 
coccus in  the  meninges  and  viscera,  producing  a  series 
of  constitutional  symptoms;  second,  decomposition 
products  resulting  from  the  disintegration  of  nervous 
tissue,  which  are  thrown  into  the  circulation;  thirdly, 
increased  intracranial  pressure. 

According  to  Kopetzky,  the  first  effect  of  the 
growth  of  the  meningococcus  in  the  meninges  is  a 
consumption  of  the  carbohydrate  of  the  cerebrospinal 
fluid  and  the  production  of  lactic  acid.  The  increased 
acidity  leads  to  oedema  of  the  nerve  tissue  and 
meninges,  and  this  is  further  increased  by  compres- 
sion of  the  nutrient  vessels.  A  change  in  the  composi- 
tion of  the  fluid  results,  which  leads  to  an  alteration 
in  its  tension  and  permeability,  and  consequent  stasis. 

Interference  with  the  metabolism  of  the  cellular 
elements  of  the  nervous  tissue  leads  to  their  de- 
generation and  the  production  of  poisonous  alkaloids, 
chiefly  cholin,  which  in  turn  act  as  nerve  poisons.  At 
a  later  stage  of  nerve  disintegration  neutral  fat  is 
formed. 

117 


118       MENINGOCOCCUS  MENINGITIS 

The  anaemia  which  results  from  compression  of 
the  centres  in  the  medulla,  as  a  result  of  the  increased 
intracranial  pressure,  acts  as  a  stimulant  to  the  vaso- 
motor centres.  The  blood-pressure  is  thus  raised,  and 
the  anaemia  temporarily  overcome.  The  changes  in 
the  respiratory  rhythm  are  chieffy  due  to  the  alternate 
increase  of  intracranial  and  blood  pressure. 

Mode  of  Onset. — In  the  vast  majority  of  cases 
the  onset  is  typically  sudden.  Even  in  infancy,  if 
sufficient  care  is  taken,  a  history  of  sudden  onset  is 
usually  obtainable.  The  abrupt  mode  of  onset  is  not 
so  seldom  the  only  clinical  feature  which  distinguishes 
this  form  of  meningitis  from  other  meningitides  of 
secondary  origin.  The  French  authors  describe  a 
fulminating  onset  in  which  the  disease  begins  with 
convulsive  seizures,  violent  delirium,  or  deep  coma, 
and  then  develops  into  an  ordinary  form  of  menin- 
gitis of  moderate  severity.  Premonitory  symptoms, 
such  as  general  malaise,  lack  of  appetite,  and  vague 
general  pains,  are  occasionally  present,  but  are 
usually  of  such  a  mild  character  that  they  pass  un- 
noticed by  the  patient.  Still  more  rare  is  the  occur- 
rence of  a  coryza,  angina,  or  otitis.  The  initial  stage 
of  the  disease  is  marked  by  three  prominent  symp- 
toms,— namely,  fever,  headache,  and  vomiting,  due 
to  absorption  of  bacterial  products  and  increased 
intracranial  pressure. 


SYMPTOMATOLOGY  119 

Vomiting  at  the  onset  is  rarely  absent  in  the  adult. 
It  is  somewhat  less  frequent  in  the  infant.  In  our 
series  of  75  children  under  13  years  of  age,  it  was 
present  in  61.  The  frequency  seems  to  increase  with 
age;  thus,  in  children  below  two  years  of  age,  it  was 
present  in  20,  absent  in  10;  above  two  years,  present 
in  41,  absent  in  only  4.  Goeppert  similarly  calls 
attention  to  the  comparative  infrequency  of  this 
symptom  in  patients  under  three  years  of  age.  At 
this  stage  it  has  the  character  of  the  vomiting  seen 
at  the  onset  of  many  acute  infectious  diseases,  and  is 
seldom  projectile  in  type. 

Headache  is  constant  in  older  patients  that  re- 
tain consciousness.  It  is  most  often  localized  in  the 
occipital  region,  and  is  of  such  an  agonizing  char- 
acter that  the  patients  often  scream  with  pain  and 
bury  the  head  in  the  pillow.  It  is  not  infrequently 
associated  with  pain  in  the  neck  and  back.  At  times 
the  pain  is  situated  in  the  frontal  and  temporal 
regions  or  diffusely  over  the  entire  cranium. 

Fever  is  seldom  absent  in  cases  with  acute  onset. 
Within  a  few  hours  it  may  mount  to  104°  or  106° 
F.  In  the  adult  it  is  quite  commonly  accompanied 
by  a  severe  chill.  In  fulminating  cases  the  prostra- 
tion is  at  times  so  great  that  there  is  no  rise  of 
temperature.  An  initial  convulsive  seizure  is  not 
unusual  in  young  children.    It  was  present  in  12  of  30 


120       MENINGOCOCCUS  MENINGITIS 

infants  below  two  years  of  age,  and  in  10  of  45  chil- 
dren between  the  ages  of  three  and  thirteen  years. 
In  adults  the  convulsive  stage  may  be  followed  by 
transitory  hemiplegia,  causing  the  physician  to  sus- 
pect the  presence  of  cerebral  hemorrhage,  embolism, 
or  thrombosis.  Increase  of  intracranial  pressure  at 
this  stage  is  usually  shown  by  the  Macewen  phe- 
nomenon, or  bulging  of  the  anterior  fontanelle. 

Delirium,  usually  of  a  mild  character,  is  another 
frequent  symptom  in  the  initial  stage.  It  is  inter- 
rupted at  frequent  intervals  by  complaint  of  intense 
headache. 

The  characteristic  symptoms  of  meningeal  in- 
volvement usually  appear  within  twenty-four  hours. 
At  times  their  appearance  is  delayed  for  several  days. 

Temperature. — Unlike  typhoid,  pneumonia,  and 
many  other  acute  infectious  diseases,  meningococcus 
meningitis  presents  no  definite  type  of  fever.  In 
fact,  cases  are  reported  in  which  an  afebrile  condition 
was  present  throughout  the  whole  course  of  the  dis- 
ease. Such  cases  are,  however,  extremely  rare.  In 
the  initial  stage,  as  we  have  seen,  the  fever  is  usually 
high.  But  cases  in  which  the  temperature  at  this 
stage  does  not  rise  above  100°  or  101°  F.  are  not  at 
all  rare.  At  times  the  temperature  drops  to  normal 
on  the  day  after  the  onset.  It  may  then  remain 
normal  for  two  or  three  days  and  then  rise  again. 


SYMPTOMATOLOGY 


121 


More  frequently,  however,  the  temperature  shows 
continuous  elevation  for  three;  four,  or  five  days 
(Fig.  11).  In  some  cases  the  temperature  is  con- 
tinuous, with  remissions  of  not  more  than  one  degree, 
resembling  the  typhoid  curve  of  the  fastigium.  In 
others  regular  daily  remissions  of  two  or  three  de- 
grees may  be  seen,  giving  the  spiked  curve  of  the 


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122       MENINGOCOCCUS  MENINGITIS 

of  antimeningitis  serum,  there  occurs  in  about  30  per 
cent,  of  the  cases  a  critical  fall  of  the  temperature. 
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of  the  other  symptoms.  The  effect  of  lumbar 
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diately  before  death,  in  acute  as  well  as  chronic  types 
of  the  disease,  the  temperature  rises  rapidly  to  105° 
or  106°  F. 

Pulse. — The  pulse  is  usually  rapid,  but  not  out  of 
proportion  to  the  temperature.  There  is  seldom  seen 
the  bradycardia  which  is  so  pronounced  a  characteris- 
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SYMPTOMATOLOGY  123 

accountable  changes  in  the  rapidity  and  character  of 
the  pulse.  In  the  course  of  a  single  examination  the 
pulse-rate  may  vary  from  60  to  130  per  minute. 

Respirations. — In  the  initial  stages  of  the  disease 
in  infants,  the  respiratory  rate  is  often  markedly  in- 
creased ( 60  to  70  per  minute )  without  there  being  any 
physical  signs  in  the  chest.  At  a  later  stage  this 
disproportionate  rapidity  of  the  respiration  dis- 
appears. At  one  time  or  another,  and  especially  in 
the  severer  cases,  the  respirations  become  irregular. 
The  irregularity  is,  however,  rarely  as  pronounced  as 
in  tuberculous  meningitis.  According  to  Conner  and 
Stillmann,  who  have  made  a  careful  pneumatographic 
study  of  the  respiratory  irregularities  in  meningitis, 
they  are  present  in  95  per  cent,  of  the  cases.  Three 
forms  of  irregularity  may  be  present, — namely, 
Cheyne-Stokes  respiration,  the  Biot  respiratory  type, 
and  undulatory  type. 

In  the  Cheyne-Stokes  type  there  are  rhythmical 
alternations  of  periods  of  respiratory  movements  with 
periods  of  apncea.  The  respiratory  periods  are  of 
approximately  equal  length  and  composed  of  the 
same  number  of  individual  respirations.  The  dura- 
tion of  the  pause  equals  V2  to  %  of  the  respiratory 
period.  In  infants  and  young  children,  the  duration 
of  each  is  much  less,  and  the  number  of  respirations 
making  up  the  respiratory  period  much  smaller.   The 


124       MENINGOCOCCUS  MENINGITIS 

period  of  apnoea  is  relatively  longer,  being  about 
equal  in  duration  to  the  respiratory  rhythm. 

Biot  first  described  the  type  of  respiration  named 
after  him  in  1876,  and  more  elaborately  in  1878.  It 
has  the  following  characteristics: 

Periods  of  apnoea  of  varying  lengths,  occurring 
at  irregular  intervals. 

Constant  irregularity  in  rhythm  and  force  of  the 
individual  respirations. 

Frequent  deep  sighing  respirations.  (This  is  a 
striking  feature  of  the  Biot  type. ) 

Conner  and  Stillmann  found  the  Biot  type  twice 
as  frequently  in  the  adult  as  in  the  child,  while  the 
Cheyne-Stokes  type  was  seen  by  them  twice  as  often 
in  children. 

In  the  undulatory  type  no  periods  of  apnoea  are 
present,  but  there  are  wave-like  variations  in  the 
depth  of  inspiration,  muscular  tonus,  or  frequency 
of  respirations. 

Very  few  of  the  meningitis  patients  failed  to  show 
this  type  at  one  or  another  time.  The  Biot  type  is 
most  pathognomonic  of  meningitis.  It  is,  however, 
seen  only  in  the  very  grave  cases.  The  presence  of 
Cheyne-Stokes  respiration  in  children  is  strongly 
suggestive  of  meningitis. 

General  Appearance  and  Attitude. — The  face  is 
usually  flushed  and  the  expression  often  bright  and 


SYMPTOMATOLOGY  125 

anxious.  Young  patients  show  signs  of  suspicion  or 
anxiety,  due  to  the  fear  of  being  disturbed.  This  is 
in  marked  contrast  to  the  "  absent "  look  seen  fre- 
quently in  tuberculous  meningitis.  Evanescent  flush- 
ing or  pallor  of  the  face  due  to  vasomotor  instability 
is  often  observed  in  the  various  stages  of  the  disease. 
The  conjunctiva  are  usually  clear,  occasionally 
suffused.  The  patients  lie  on  the  side,  as  in  this 
position  there  is  less  pressure  on  the  back  of  the 
head.  When  prostration  is  marked  and  coma  super- 
venes, the  patients  often  lie  relaxed  on  the  back. 

Mental  Condition. — In  contrast  to  other  forms 
of  meningitis,  tuberculous  meningitis  in  particular, 
the  mind  is  at  times  perfectly  clear.  Even  during 
periods  of  confusion  the  patients  can  be  aroused 
sufficiently  to  answer  questions  fairly  intelligently. 
Loss  of  consciousness  in  children  below  three  years 
of  age  is  rare.  Marked  restlessness  and  irritability 
are  frequent  in  this  type  of  meningitis.  The  patients 
often  toss  about  for  hours  at  a  time.  Insomnia  is  an 
annoying  symptom  of  great  frequency,  and  is  partly 
due  to  the  headache  which  shows  nocturnal  exacerba- 
tions. Paroxysmal  delirium  is  frequent.  It  is  often 
of  a  mild  grade;  at  times,  however,  it  becomes  mania- 
cal in  character.  At  the  terminal  stage  and  in 
malignant  types  of  the  disease,  the  patients  fall  into 
deep   coma.      The   chronic   stage   of   the   disease    is 


126       MENINGOCOCCUS  MENINGITIS 

marked  by  apathy,  lack  of  interest  in  the  surround- 
ings, and  at  times  stupor.  The  last  symptom  usually 
develops  with  increasing  hydrocephalus. 

Ocular  Symptoms.  —  The  frequency  of  these 
symptoms  varies  greatly  with  each  epidemic.  It  is 
probable  that  in  the  past  these  symptoms  have  fre- 
quently been  overlooked,  as  they  are  often  present 
only  during  a  short  period  of  the  disease. 

The  following  table,  taken  partly  from  Goeppert, 
gives  the  observation  of  a  number  of  clinicians  who 
have  paid  special  attention  to  this  phase  of  the 
symptomatology  of  the  disease: 


Uthoff 
(160  cases). 


Heine 
(160  cases). 


Goeppert 
(150  cases). 


Ballantyne 
(73  cases). 


Changes  in  pupils 

Di  sturbances   of   ocular 

muscles 

Nystagmus 

Optic  neuritis 


p.  ct. 

12  =  11 

16  =  15 

8=7 

18  =  16 


p.  ct. 


7  =  7 
3=3 


p.  ct. 

37  =  24 
17  =  12 


p.  ct. 

63  of  69  =  91 

23     =  31 

7     =  9  + 
5  of  61  =8 


Changes  in  the  Pupils. — These  are  the  most 
common  of  the  eye  symptoms  of  the  disease.  In- 
equality of  the  pupils  is  very  frequent  in  the  first 
few  days.  More  or  less  mydriasis  is  present  in  more 
than  half  of  the  cases  during  the  height  of  the  disease. 
The  size  of  the  pupils  changes  greatly  from  time  to 
time.  Myosis  is  usually  present  during  a  convulsive 
seizure.     Rhythmic  changes  in  the  pupils  which  are 


SYMPTOMATOLOGY  127 

independent  of  the  illumination  or  distance  of  the 
focused  object  (hippus)  are  frequently  seen.  We 
have  often  observed  sudden  dilatation  of  the  pupils 
when  the  attempt  is  made  to  flex  the  head  on  the 
chest.  In  severe  cases  Goeppert  has  observed  dilata- 
tion of  the  pupils  on  irritating  the  skin.  Its  presence 
in  the  earlier  stages  of  the  disease  he  considers  to  be 
of  grave  omen.  In  deep  coma  the  light  reflex  is 
frequently  lost. 

Disturbances  of  the  Ocular  Muscles. — Strabismus 
is  the  most  common  of  these  disturbances.  Goeppert 
is  of  the  opinion  that  unilateral  convergent  strabis- 
mus is  present  at  one  time  or  another  in  one-third 
of  the  cases  during  the  first  three  days  of  the  disease. 
In  our  own  cases  strabismus  was  present  in  12  of  30 
infants  below  two  years  of  age,  and  in  22  of  45  chil- 
dren between  three  and  thirteen  years  of  age.  Unlike 
that  of  tuberculous  meningitis,  the  strabismus  is 
rarely  paralytic  in  nature.  It  varies  greatly  from 
time  to  time;  occasionally  a  convergent  is  changed 
directly  into  a  divergent  squint.  Nystagmus  seems 
to  occur  more  frequently  in  severe  cases.  It  was 
present  in  9  of  75  of  our  patients.  At  times  con- 
jugate deviation  of  the  eyes  is  present.  This  symp- 
tom is  often  observed  during  and  after  a  convulsive 
seizure. 

Optic  Nerve  Changes. — Optic  neuritis  is  much 


128       MENINGOCOCCUS  MENINGITIS 

less  frequent  than  in  tuberculous  meningitis.  In  our 
cases  it  was  rather  unusual  to  find  marked  changes  in 
the  disk  during  the  acute  stage  of  the  disease.  Simi- 
larly Matthes  found  no  changes  in  the  fundus  in  35 
cases.  According  to  Netter  and  Debre,  papillitis  is 
frequent  at  the  height  of  the  disease.  It  is  bilateral 
and  usually  of  short  duration.  In  most  of  the  cases 
they  did  not  observe  any  change  in  the  acuity  of 
vision. 

Sensory  Disturbances. — The  most  frequent  sub- 
jective disturbances  are  headache,  hyperesthesia,  and 
pains  in  various  parts  of  the  body.  In  the  acute  stage 
the  headache  is  almost  constant,  though  marked  by 
nocturnal  exacerbations.  At  times  the  torture  pro- 
duced by  this  symptom  is  almost  unendurable.  On 
its  appearance,  otherwise  stoical  individuals  often  cry 
like  babies  or  attempt  self-destruction.  The  site  of 
the  pain  varies ;  most  often  it  is  localized  in  the  occi- 
pital region.  In  the  chronic  stage  it  is  not  infre- 
quently paroxysmal  in  character  and  is  accompanied 
by  elevation  of  temperature  and  vomiting. 

Hyperesthesia  is  a  cardinal  symptom,  rarely 
absent  in  conscious  patients.  They  are  very  sensitive 
to  light  and  to  loud  sounds.  Ker  observed  in  many 
patients  an  extraordinary  sensitiveness  to  cold.  The 
hyperesthesia  is  most  pronounced  along  the  spine 
and  is  often  much  relieved  by  lumbar  puncture.    In 


SYMPTOMATOLOGY  129 

young  children  Goeppert  has  observed  a  series  of 
cases  in  which  hyperesthesia  of  the  lower  extremities 
on  passive  motion  was  an  early  and  pronounced 
symptom. 

Spontaneous  pain  in  the  extremities  is  often 
present.  It  is  in  part  due  to  pressure  of  the  in- 
flammatory exudate  on  the  spinal  roots.  It  may  be 
felt  as  shooting  pains  along  the  course  of  the  nerves. 
In  other  cases  it  is  localized  in  the  muscles  or  joints. 
Despite  the  marked  rigidity  of  the  spine,  spontaneous 
pain  in  this  region  is  rarely  very  severe.  At  times 
reflected  pain  is  present  along  the  front  of  the  neck, 
thorax,  and  abdomen. 

Motor  Disturbances. — Convulsions  are  rare  in  the 
adult.  Typical  epileptiform  attacks  may,  however, 
be  seen  in  grave  cases.  At  times  status  epilepticus 
develops,  leading  rapidly  to  a  fatal  termination.  In 
rare  cases  paroxysmal  attacks  of  tetany  occur,  with 
spasmodic  retraction  of  the  head,  marked  opistho- 
tonus, rigid  extension  of  the  arms,  and  clenching  of 
the  fists.  Tremor  of  the  hands  from  the  earliest 
stages  of  the  disease  was  often  observed  by  us  in 
young  patients.  Twitching  of  the  lids,  athetoid 
movements,  munching  and  sucking  motions,  spas- 
modic shaking  of  the  head,  subsultus  tendinum,  and 
carphologia  are  occasionally  seen  in  children. 

Reflexes. — The  deep  reflexes  are  at  times  difficult 


130       MENINGOCOCCUS  MENINGITIS 

to  obtain,  on  account  of  the  hyperesthesia  and  rigidity 
of  the  limbs.  The  knee-jerk  was  present  in  21  and 
active  in  15  of  the  45  cases  between  three  and  thirteen 
years  of  age.  The  superficial  reflexes  are  usually  pre- 
served in  the  early  stages  of  the  disease.  Both  the 
deep  and  superficial  reflexes  usually  disappear  in  the 
rapidly  fatal  or  moribund  cases.  Ankle-clonus  was 
never  observed  by  us. 

The  Babinski  reflex  (Fig.  13),  (extension  of  the 
great  toe  following  irritation  of  the  plantar  surface 
of  the  foot)  is  of  little  value  in  children  below  two 
years  of  age,  as  it  is  often  seen  in  perfectly  normal 
infants.  It  was  present  on  one  or  both  sides  in  24 
out  of  45  children  above  two  years  of  age.  Other 
observers  have  found  it  rather  less  frequently.  At 
any  rate,  it  occurs  less  often  than  in  tuberculous 
meningitis,  where  Koplik  found  a  positive  reaction 
in  77  per  cent,  of  his  cases. 

The  Oppenheim  reflex  (extension  of  the  great 
toe  following  vigorous  rubbing  along  the  inner  sur- 
face of  the  tibia)  is  apparently  much  less  frequent 
in  these  cases  than  the  Babinski,  as  it  was  present  in 
only  2  out  of  45  of  the  older  children. 

Vasomotor  and  Trophic  Disturbances. — Tache 
cerebrale  is  seen  frequently,  but  is  not  of  very  great 
value  in  diagnosis.  When  the  nail  is  drawn  across  the 
skin,  there  appears  a  red  line  having  no  definite  bor- 


iuiiiiiiL:  mi 


Fig.   L3.  —  Babinski  ~it:n. 


SYMPTOMATOLOGY  131 

ders  or  one  limited  on  each  side  by  a  white  line.  In 
meningitis  it  is  characterized  by  the  rapidity  of  its 
appearance,  intensity,  and  persistence.  In  the  course 
of  the  disease  the  skin  often  becomes  suddenly  flushed 
or  covered  with  perspiration.  Evanescent  localized 
erythema  also  occurs  quite  frequently.  The  pro- 
gressive emaciation,  which  is  so  constant  and  striking 
a  feature  of  the  cases  running  a  chronic  course,  is  due 
for  the  most  part  to  trophic  disturbances. 

Rigidity  of  the  Neck. — This  is  the  cardinal  symp- 
tom of  meningeal  irritation  or  infection.  It  is  present 
to  a  greater  or  less  extent  in  nearly  all  forms  of 
meningitis.  In  very  young  or  very  old  patients,  and 
in  those  who  are  in  a  condition  of  collapse  or  deep 
coma,  rigidity  of  the  neck  is  likely  to  be  absent.  To 
detect  slight  degrees  of  rigidity,  the  head  should  be 
placed  in  the  hollow  of  the  hand  and  moved  gently 
in  all  directions.  It  is  of  the  utmost  importance  in 
children  not  to  mistake  voluntary  resistance  for  true 
rigidity.  Voluntary  resistance  of  the  neck  varies 
from  one  moment  to  another  and  is  apt  to  disappear 
in  the  course  of  a  single  examination.  True  rigidity, 
on  the  other  hand,  usually  becomes  more  pronounced 
with  the  repetition  of  the  manipulations  employed 
for  eliciting  it.  Moreover,  it  gives  the  experienced 
examiner  the  impression  as  though  the  cervical  verte- 
bras were  soldered  together.    To  acquire  skill  in  the 


132       MENINGOCOCCUS  MENINGITIS 

detection  of  slight  degrees  of  rigidity  constant  prac- 
tice in  the  examination  of  many  sick  and  healthy 
infants  is  essential. 

With  the  advent  of  specific  serotherapy  and  the 
supreme  importance  of  its  early  employment  in  the 
proper  cases,  the  detection  of  the  earliest  traces  of 
rigidity  becomes  a  matter  of  the  greatest  moment. 
On  its  demonstration  often  hinges  the  sole  indication 
for  the  diagnostic  procedure  of  lumbar  puncture. 

It  is  equally  important  to  remember  that  in  some 
cases  the  rigidity  is  not  present  at  all  times.  Fre- 
quent examination  for  this  symptom  is  therefore 
necessary  in  cases  where  the  slightest  suspicion  of  the 
presence  of  meningitis  is  entertained.  The  accentua- 
tion of  this  symptom  at  the  end  of  repeated  manipula- 
tions at  times  permits  its  visual  detection  if  the 
patient  is  completely  uncovered  and  placed  on  a 
flat  surface.  Rigidity  of  the  neck  was  present  at  one 
time  or  another  in  26  of  30  infants  below  two  years 
of  age,  and  in  43  of  45  children  between  the  ages'  of 
three  and  thirteen  years.  Goeppert  describes  a 
number  of  cases  in  young  infants  in  which  this  symp- 
tom was  absent  during  the  whole  course  of  the  dis- 
ease. In  contrast  to  the  marked  Kernig  usually 
present  in  old  people,  the  rigidity  of  the  neck  is 
slightly  marked  or  entirely  absent.  In  the  stormy 
course  of  the  cases  belonging  to  the  fulminating  type, 


I 


Fig.  14.  —  Kernig  sign. 


^■—W w0*m*mmmMm     t\  nil  tm    mi  ■■  w 


I'  n,.   !  "i      Kernig  sign. 


Fig.   16. — Brudzinski  signs. 


SYMPTOMATOLOGY  133 

death  may  take  place  before  this  symptom  has  had 
time  to  develop. 

The  Kernig  Sign  (Figs.  14  and  15). — This  sign, 
which  was  first  described  by  Kernig  in  1882,  shares 
equal  importance  with  the  neck  rigidity  as  a  diag- 
nostic feature  of  the  disease.  It  is  present  to  a  more 
or  less  marked  degree  in  all  forms  of  meningitis.  By 
itself  it  is  not  a  pathognomonic  sign  of  meningeal 
inflammation,  as  it  is  occasionally  present  in  menin- 
geal hemorrhage  as  well  as  in  acute  febrile  diseases 
accompanied  by  meningeal  irritation  or  so-called 
meningism.  In  the  opinion  of  a  number  of  authori- 
ties, the  Kernig  sign  appears  somewhat  earlier  than 
the  rigidity  of  the  neck.  This,  however,  may  be  due 
to  the  fact  that  the  Kernig  sign,  even  when  only 
slightly  marked,  is  more  readily  recognized  than 
slight  degrees  of  rigidity  of  the  neck. 

The  test,  as  originally  described  by  Kernig,  is 
carried  out  as  follows:  The  patient  is  propped  up  in 
bed  in  the  sitting  posture  with  the  thighs  flexed  at  a 
right  angle  to  the  abdomen.  When  the  sign  is 
present,  the  legs  will  be  found  flexed  at  the  knees, 
and  reasonable  attempts  by  the  physician  at  complete 
extension  at  the  knees  will  fail  unless  the  back  of  the 
patient  is  lowered  and  the  angle  at  the  hip  thus  made 
more  obtuse.  On  account  of  the  difficulty  often  en- 
countered in  this  disease  in  sitting  the  patient  up  in 


134       MENINGOCOCCUS  MENINGITIS 

bed,  Osier  has  proposed  a  useful  modification  of  the 
method  of  carrying  out  the  test.  It  consists  in  flex- 
ing the  thighs  on  the  abdomen  at  a  right  angle  while 
the  patient  is  lying  in  bed  in  the  horizontal  position. 
When  the  sign  is  present,  complete  extension  of  the 
legs  at  the  knees  is  impossible.  Another  variation  of 
this  test  consists  in  the  determination  of  the  degree 
of  angular  flexion  obtainable  at  the  hip  with  the  leg 
in  complete  extension  at  the  knee.  In  cases  where  the 
sign  is  present,  this  angle  under  the  conditions  of  the 
test  is  never  less  than  90°.  These  modifications  are 
now  generally  employed  in  America,  and  seem  to 
yield  results  which  are  practically  identical  with  those 
obtainable  with  the  test  carried  out  according  to  the 
original  directions  of  Kernig. 

Unfortunately,  this  important  sign  is  of  practi- 
cally no  value  in  children  below  two  years  of  age. 
This  is  attributable  to  the  rigidity  of  the  legs  which 
is  usually  present  at  this  age  and  to  the  fact  that  in 
normal  infants  there  often  exists  a  physiologic  myo- 
tonia which  may  yield  a  positive  Kernig  sign.  The 
Kernig  sign  was  present  in  37  of  45  children  above 
two  years  of  age.  This  sign,  when  present,  is  almost 
always  bilateral.  It  at  times  persists  long  after  all 
other  symptoms  have  disappeared.  Goeppert  re- 
lates a  case  where  it  persisted  in  a  marked  form  as 
the  only  symptom  for  twenty-eight  days  after  con- 
valescence was  apparently  complete. 


SYMPTOMATOLOGY  135 

While  a  number  of  hypotheses  have  been  ad- 
vanced in  explanation  of  this  phenomenon,  none  that 
is  adequate  is  at  hand.  It  can  not  merely  be  due  to 
increased  pressure  in  the  subarachnoid  space,  as  it 
often  persists  after  lumbar  puncture.  The  most 
probable  explanation  is  that  it  is  due  to  irritation  of 
the  nerve-roots  which  leads  to  contracture  of  the 
flexor  muscles  of  the  legs.  As  normally  when  the 
thigh  is  flexed  on  the  pelvis,  and  the  leg  extended 
fully  at  the  knee,  these  muscles  are  stretched  to  the 
limit  of  their  elasticity,  a  slight  contracture  becomes 
readily  evident. 

Brudzinski  Neck  and  Leg  Signs  (Fig.  16). — In 
1908  this  observer  described  the  presence  in  menin- 
gitis of  a  sign  which  he  called  the  contralateral  re- 
flex. On  passive  flexion  of  the  leg  on  one  side,  there 
is  either  flexion  of  the  other  leg  (identical  contra- 
lateral reflex)  or  extension  of  the  other  leg  (recipro- 
cal contralateral  reflex).  In  1909  the  same  observer 
described  the  neck  sign  which  is  shown  in  flexion  of 
the  legs  on  passive  flexion  of  the  head  and  neck. 
In  42  cases  of  meningitis,  Brudzinski  found  the  neck 
sign  in  97  per  cent.,  the  contralateral  leg  reflex  in 
66  per  cent.,  while  the  Kernig  was  present  in  only 
57  per  cent,  of  the  cases. 

Greco  and  Zaimovsky  confirmed  the  observations 
of  Brudzinski.  Greco  was  unable  to  detect  it  in 
conditions  other  than  meningitis,  while  Zaimovsky 


136       MENINGOCOCCUS  MENINGITIS 

found  it  almost  constant  in  this  disease.  In  400  chil- 
dren either  perfectly  well  or  suffering  from  disease 
other  than  meningitis,  Morse  did  not  find  either  the 
neck  or  leg  signs.  In  meningitis  this  observer  found 
the  neck  sign  more  frequent  than  the  leg  sign.  It  is, 
however,  present  in  all  forms  of  meningitis,  and  is 
consequently  of  no  value  in  the  differentiation  be- 
tween the  various  forms  of  this  disease.  Its  absence, 
on  the  other  hand,  does  not  exclude  the  existence  of 
a  meningitis. 

Brudzinski  attributes  the  neck  sign  to  muscular 
hypertonus  of  the  legs  and  to  physiologic  predomin- 
ance of  the  extensor  muscles  of  the  neck  and  back 
over  the  flexor  muscles  of  the  legs.  The  contralateral 
leg  sign  is  attributed  to  a  reversion  in  meningitis  to 
an  earlier  state  of  fetal  life  in  which  there  exists 
bilateral  innervation  and  anatomical  connection  be- 
tween the  centres  of  corresponding  muscles  of  each 
leg. 

Opisthotonus. — This  symptom  occurs  in  about  70 
per  cent,  of  juvenile  patients.  In  the  adult  it  is  much 
less  frequent.  It  produces  arching  of  the  back  so  that 
the  two  points  of  contact  with  the  bed  are  the  occiput 
or  vertex  and  the  lumbosacral  region.  When  the 
hand  is  placed  under  the  head,  the  whole  body  moves 
in  a  statuesque  condition.  As  has  been  seen,  opistho- 
tonus is  a  prominent  symptom   of  posterior  basic 


SYMPTOMATOLOGY  137 

meningitis  and  is  chiefly  instrumental  in  the  produc- 
tion of  the  characteristic  deformity  of  the  disease. 
As  Busse  has  suggested,  this  symptom  is  probably 
due  to  the  fact  that  when  the  back  is  arched  the 
capacity  of  the  subarachnoid  space  is  increased.  This 
seems  to  be  borne  out  by  the  common  observation 
that,  when  the  head,  neck,  and  back  are  flexed  during 
lumbar  puncture,  the  flow  of  cerebrospinal  fluid  tends 
to  increase. 

Retraction  of  the  Head. — Retraction  of  the  head 
is  not  very  common  in  the  adult  patient.  It  is  more 
frequent  in  children,  and  is  a  constant  and  pro- 
nounced feature  in  cases  belonging  to  the  posterior 
basic  type. 

Rigidity  in  other  parts  of  the  body  occurs  much 
less  frequently.  Occasionally  rigid  contraction  of  the 
upper  extremity  is  seen.  Still  more  rare  is  con- 
tracture of  the  masseters  producing  trismus,  or  con- 
tractures of  the  facial  muscles  causing  risus  sardoni- 
cus.  At  times  spasmodic  contraction  of  the  muscles 
of  the  extremities  produces  a  picture  closely  simulat- 
ing the  characteristic  attitude  of  tetany. 

Fontanelles  and  Sutures. — The  condition  of  the 
anterior  fontanelle  in  young  children  is  of  the  great- 
est diagnostic  importance.  In  the  early  stages  of  the 
disease  it  is  often  tense  and  bulging;  in  the  second 
and  third  week,  however,  it  becomes  depressed,  even 


138       MENINGOCOCCUS  MENINGITIS 

in  those  cases  that  later  end  fatally.  With  the  bulg- 
ing of  the  fontanelle  there  is  not  infrequently  asso- 
ciated a  separation  of  the  sutures.  This  symptom 
Goeppert  found  in  13  of  34  infants.  At  times  the 
heightened  intracranial  pressure  leads  to  a  reopening 
of  the  posterior  fontanelle.  There  is  occasionally 
overriding  of  the  occipital  by  the  parietal  bones,  due 
to  the  greater  mobility  of  the  latter.  With  a  high 
grade  of  hydrocephalus,  the  veins  of  the  scalp  be- 
come dilated  and  prominent. 

Macewen  Sign. — In  conditions  in  which  there  is 
accumulation  of  fluid  in  the  lateral  ventricles,  Mac- 
ewen has  shown  that  percussion  over  the  anterior 
horn  of  the  ventricle  yields  a  hollow  note.  The  sign 
is  best  obtained  by  sitting  the  patient  upright  and 
inclining  the  head  to  one  side,  thus  placing  the  in- 
ferior portions  of  the  frontal  or  parietal  bones 
directly  under  the  anterior  horn  of  the  ventricle.  As 
it  indicates  fluid  under  tension,  the  sign  is  manifestly 
not  to  be  expected  in  infants  that  have  still  open 
fontanelles.  It  was  present  in  35  of  45  children 
above  two  years  of  age. 

Gastro-intestinal  Disturbances. — Vomiting,  as  we 
have  observed,  is  practically  always  present  in  the 
adult  and  older  children  at  the  onset.  It  appears 
unexpectedly  and  is  seldom  preceded  by  nausea.  The 
vomitus  consists  of  undigested  food  or  yellow  fluid. 


SYMPTOMATOLOGY  139 

In  this  form  of  meningitis  it  is  less  often  projectile 
than  in  tuberculous  meningitis.  It  usually  disap- 
pears soon  after  the  onset,  and  does  not  recur  except 
in  the  protracted  cases;  in  these,  paroxysmal  attacks 
of  vomiting  occur  from  time  to  time.  In  some  cases 
it  becomes  a  serious  symptom,  as  it  interferes  seri- 
ously with  the  taking  of  food.  In  the  great  majority 
of  meningitis  patients  the  bowels  act  normally. 
Occasionally  constipation  is  present;  still  less  often 
does  persistent  diarrhoea  occur.  In  infancy  the  dis- 
ease may  begin  with  abdominal  pain  and  diarrhceal 
stools.  The  appetite,  as  a  rule,  is  good.  The  patients 
often  exhibit  marked  thirst  throughout  the  disease. 

Cutaneous  Manifestations. — These  vary  markedly 
with  the  character  of  the  epidemic.  In  the  early  epi- 
demics in  America  the  rash  was  so  prominent  a 
feature  of  the  disease  that  it  went  commonly  under 
the  name  of  "  spotted  or  black  fever."  The  epidemics 
in  Ireland  and  Sweden  were  also  characterized  by 
great  frequency  of  the  rash.  In  the  recent  epidemic 
in  Xew  York,  however,  skin  eruptions  were  generally 
absent. 

Herpes  occurs  even  more  frequently  in  this  dis- 
ease than  in  pneumonia.  It  is,  however,  rare  in 
patients  under  two  years  of  age.  It  was  present  in 
only  1  out  of  30  patients,  whereas  amongst  45  chil- 
dren above  two  years  of  age  it  occurred  in  12  cases. 


140       MENINGOCOCCUS  MENINGITIS 

Between  the  second  and  sixth  days  of  the  disease 
Goeppert  found  herpes  in  60  per  cent,  of  the  children, 
but  not  once  in  children  under  three  years  of  age. 
According  to  Einhorn,  the  herpetic  eruption  of  this 
disease  is  characterized  by  great  severity,  wide  dis- 
tribution, unusual  localization,  occurrence  in  crops, 
prolonged  duration  and  slow  healing.  It  is  rarely 
seen  before  the  second  or  third  day  of  the  disease. 
Most  often  it  appears  at  the  end  of  the  first  week. 
Its  site  is  variable  and  it  may  cover  a  comparatively 
large  surface  of  the  body.  As  in  pneumonia,  it  occurs 
most  frequently  on  the  face  about  the  lips  and  nose.  It 
has,  however,  been  seen  on  the  tongue,  gums,  palate, 
conjunctivae,  ends  of  the  fingers  and  toes,  vulva  and 
anal  region.  As  a  rule  the  vesicles  are  small,  but 
occasionally  giant  forms  may  be  seen.  In  one  case 
at  the  hospital  the  presence  over  an  extensive  area 
of  a  number  of  vesico-pustules  aroused  for  a  time 
suspicion  of  the  existence  of  variola.  Occasionally 
extensive  ulceration  occurs.  Typical  herpes  zoster  is 
but  seldom  seen. 

A  sparse  roseolar  eruption,  not  unlike  that  seen 
in  typhoid  fever,  occurs  in  a  small  proportion  of  the 
cases  in  the  first  few  days  of  the  disease.  In  the 
second  and  third  weeks  a  more  wide-spread  morbilli- 
form or  scarlatinaform  eruption  is  occasionally  seen. 
They  usually  occur  on  the  flexor  aspects  of  the  ex- 
tremities and  the  lower  abdomen,  and  fade  rapidly. 


SYMPTOMATOLOGY  141 

Hemorrhagic  rashes  occur  either  in  the  form  of  a 
petechial  or  purpuric  eruption.  On  the  first  few  days 
they  are  usually  seen  on  the  abdomen,  thorax,  and 
inner  aspect  of  the  thighs,  as  numerous  small  spots 
resembling  flea-bites  or  larger  blotches  with  indefinite 
borders,  maroon  or  purple  in  color.  At  times  there  is 
(Edematous  infiltration  of  the  overlying  skin.  In 
severe  cases  large  subcutaneous  hemorrhages  may 
appear,  at  times  associated  with  hemorrhages  in  the 
kidneys,  intestines,  thorax,  and  joints.  In  the  ter- 
minal period  of  the  chronic  stage,  the  abdomen  may 
be  covered  with  dark  red  hemorrhagic  blotches,  vary- 
ing in  size  from  a  millet-seed  to  a  hemp-seed. 

Petechia?  are  more  common  in  older  children  than 
in  infants.  Recently,  however,  several  infants  with 
petechia?  were  admitted  to  the  Mt.  Sinai  Hospital. 
In  children  above  two  years  of  age  petechia?  were 
encountered  in  about  16  per  cent,  of  the  cases. 

Osier  has  described  a  peculiar  diffuse  livid  eryth- 
ema about  the  extensor  surfaces  of  the  joints  of  the 
extremities  which  was  accompanied  by  vesicles  filled 
with  blood.  After  the  erythema  faded  and  the 
vesicles  dried,  small  nodules  persisted  for  a  week  or 
ten  days. 

The  Urine.  —  Albuminuria,  casts,  and  renal 
elements  are  not  frequent.  Among  66  cases,  a  heavy 
trace  of  albumin  and  casts  were  present  in  2,  faint 


142       MENINGOCOCCUS  MENINGITIS 

trace  of  albumin  in  3 ;  in  all  the  others  the  urine  was 
chemically  and  microscopically  negative.  Hema- 
turia, invariably  associated  with  purpura,  is  at  times 
present  in  malignant  cases.  The  French  observers, 
Loeper  and  Gouraud,  describe  a  urinary  syndrome 
or  meningitic  diabetes  characterized  by  polyuria  and 
increased  excretion  of  nitrogen,  phosphates,  and 
chlorides.  They  attribute  this  condition  to  probable 
irritation  of  the  floor  of  the  fourth  ventricle. 

The  Blood.  —  An  unmistakable  polynuclear 
leucocytosis  is  a  well-nigh  constant  feature  in  this 
disease.  It  is  present  in  mild  as  well  as  in  severe 
cases  during  the  acute  stage,  and  usually  also  in  the 
chronic  stage.  The  degree  of  leucocytosis  offers  no 
prognostic  data  of  importance,  as  it  often  varies  un- 
accountably from  day  to  day.  The  following  table 
shows  the  average  leucocyte  count  in  our  patients 
below  fifteen  years  of  age. 


9,000 
10-15,000 
15-20,000 
20-25,000 
25-30,000 
30-40,000 
40-50,000 
50-60,000 
60-70,000 


per  cubic 
per  cubic 
per  cubic 
per  cubic 
per  cubic 
per  cubic 
per  cubic 
per  cubic 
per  cubic 


millimetre . 
millimetre . 
millimetre . 
millimetre . 
millimetre . 
millimetre, 
millimetre . 
millimetre, 
millimetre . 


Below  2  years 
of  age. 


2  patients 

3  patients 
7  patients 
5  patients 

4  patients 
1  patient 
1  patient 


1  patient 
(63,000) 


Above  2  years 
of  age. 


1  patient 
4  patients 
9  patients 
13  patients 
8  patients 
4  patients 
4  patients 
1  patient 
1  patient 
(73,000) 


SYMPTOMATOLOGY  143 

The  minimum  leucocyte  count  was  9000  per  cubic 
millimetre,  the  maximum  63,000  and  73,000  per  cubic 
millimetre. 

In  fulminating  cases  the  eosinophiles  regularly 
disappear  from  the  blood.  The  presence  in  the  blood 
of  meningococci,  specific  agglutinins,  and  high 
opsonic  index  will  be  discussed  in  the  chapter  on 
Diagnosis. 

Blood-pressure. — Robinson  found  a  moderate 
increase  in  blood-pressure  in  the  early  acute  stage, 
during  an  exacerbation,  and  at  an  advanced  stage  of 
the  disease.  There  is  usually  a  fall  of  blood-pressure 
after  lumbar  puncture,  but  the  effect  of  this  pro- 
cedure on  the  pressure  is  not  constant.  During  con- 
valescence the  blood-pressure,  as  a  rule,  is  low.  With 
obliteration  of  the  foramina  of  the  fourth  ventricle 
and  the  development  of  hydrocephalus,  the  blood- 
pressure  increases  with  the  increase  in  intracranial 
pressure. 

Relapses. — Relapses  are  quite  common  and  may 
appear  after  the  lapse  of  a  considerable  period  of 
normal  temperature  and  complete  absence  of  acute 
symptoms.  Ker  has  seen  relapses  in  15  to  20  per  cent, 
of  his  cases.  On  the  other  hand,  Goeppert  contends 
that  true  relapses  are  rare.  Among  136  convalescents 
he  saw  this  condition  only  twice.  But  he  does  not 
consider  a   patient   convalescent   until   the   Kernig, 


144       MENINGOCOCCUS  MENINGITIS 

ankle-clonus,  and  change  in  disposition  have  disap- 
peared. In  the  literature  cases  are  reported  in  which 
relapses  have  occurred  as  late  as  four  months  after 
the  acute  disease.  It  often  appears  suddenly  without 
any  apparent  exciting  cause.  There  may  be  a  repeti- 
tion of  all  the  initial  symptoms.  Fever,  headache, 
rigidity,  and  even  herpes  may  appear  once  more. 
These  symptoms  usually  disappear  in  a  few  days. 
With  repetition  of  relapses  the  case  may  assume  a 
chronic  course.  While  in  most  cases  the  relapse  is 
milder  than  the  original  attack,  cases  are  not  at  all 
rare  in  which  fatal  relapses  have  been  seen. 

Convalescence. — The  character  of  the  convales- 
cent period  has  fortunately  changed  since  the  adop- 
tion of  serotherapjr,  and  the  description  in  the  older 
books  no  longer  applies  to  many  of  the  cases.. 
Formerly  it  was  often  extremely  tedious.  Since  the 
inauguration  of  specific  therapy  it  is  not  infrequently 
surprisingly  rapid.  Quite  often  there  is  a  critical 
fall  in  the  temperature  and  most  of  the  other  symp- 
toms; the  headache,  hyperesthesia,  irritability,  and 
sleeplessness  disappear  within  a  few  days.  The  rigid- 
ity of  the  neck,  and  particularly  the  Kernig  sign, 
persist  for  perhaps  a  week  or  more.  On  first  getting 
out  of  bed  the  patient  may  complain  of  stiffness  in 
the  lumbosacral  region  and  the  gait  may  be  awkward 
and  stiff. 


Chart  II 


o»te  or 

MONTH 

Muy  13       J           14                     15 

16                      17 

18                      19 

PULSE 
RATE 

130 

HOUR 

4     3    1^4     3    12  4     3124     6  '  2 1 4  '  8   12    4     S   12|  4 

3    124      s    12    4     3124     8    12 

4'8    12    4     e   1i    4     3  12    4     3  1* 

—f— —!—*-*- — 

— 

104 

iiorf 

< 

£  102' 

3 

~- — r 

-   — — 

I  I  I  1   1   1   1 1 Mil 1 |_j I 1   i   1 1 1   I 

: 

nrfWlll  1 1 1 1 1 1 1 1 1 1 1 

i — ' ' — '' — 1 

120 

::~  -"--- 1 

— ;    ;  - : 

110 

2101° 

£  ioo 

~ 

\\r\\  1  1  i  h       '  -^ 

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100 
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;  :^.^/:  ~'£&~T- 

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PULSE 

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*■ 

f. 

a  ■-  - 

Critical  Fall  in  the  Temperature  Caused  by  Serum  Injecti 


SYMPTOMATOLOGY  145 

Recovery  from  the  chronic  stage  takes  place  very 
slowly.  The  muscles  of  the  neck  show  temporary 
paresis,  the  patient  being  unable  to  hold  up  the  head 
in  the  sitting  posture.  General  feebleness  and  ema- 
ciation persist  for  many  weeks.  The  patient  may 
exhibit  a  train  of  psychic  symptoms.  Temporary 
forgetfulness  and  loss  of  mental  concentration  are 
often  present  in  adult  convalescents.  Children  quite 
frequently  become  peevish  and  suffer  from  sudden 
fits  of  unprovoked  anger.  These  symptoms  will  be 
described  in  greater  detail  in  the  section  devoted  to 
the  Sequelae  of  the  disease. 

Bibliography 
Stille:    Epidemic  Meningitis,  Phila.,  1867. 
Biot:      Etude    clinique    et    experim.    sur    la    Respiration    de 

Cheyne-Stokes,  Paris,  1878. 
Kernio;:     Berl.  klin.  Wochenschr.,  1884,  xxi,  829. 
Uhthoff:  Bericht  xxxii  Versam.  d.  Ophthal.  Gessell.,  1905,  84. 
Heine:  Berl.  klin.  Wochenschr.,  1905,  xliii,  772. 
Loeper  and  Gouraud:    La  Presse  Medicale,  1905,  xiii,  65. 
Ballantyne:  Brit.  Med.  Jour.,  1907,  ii,  190. 
Einhorn  :  Wiener  klin.  Wochenschr.,  1907,  xx,  700. 
Brudzinski:    Wiener  klin.  Wochenschr.,  1908,  xxi,  255. 
Ker:    Practitioner,  1908,  xxvii,  66. 

Edinburgh  Med.  Jour.,  1908,  N.  S.  i,  306. 
Matthes:     Med.  Klinik,  1908,  iv,  734. 
Goeppert :    Ergeb.  d.  Inner  Med.  Kinder hk.,  1909,  iv,  165. 
Brudzinski :    Arch,  de  Mc'd.  des  Enfants,  1909,  xii,  188,  745. 
10 


146       MENINGOCOCCUS  MENINGITIS 

Robinson:      Bull.   Ayer   Clinic   Lab.    Penna.    Hosp.,   Phila., 

1910,  27. 
Morse:    Arch.  Pediat.,  1910,  xxvii,  561. 
Rusco:    Deut.  Arch.  f.  klin.  Med.,  1911,  ciii,  235. 
Conner:    Amer.  Jour.  Med.  Sciences,  1911,  cxli,  350. 
Netter  and  Debre:La  Meningite  Cerebrospinal,  Paris,  1911. 
Kopetzky:     Trans.  Amer.  Laryng.,  Rhinolog.   Soc,   1912, 

118. 
Conner  and  Stillmann:     Arch.  Int.  Med.,  1912,  ix,  203. 


CHAPTER  IX 

Cerebrospinal  Fluid 

Lumbar  Puncture. — Before  describing  the  char- 
acteristics of  the  cerebrospinal  fluid  in  health  and 
disease,  we  must  enter  into  a  somewhat  detailed 
description  of  the  important  procedure  of  lumbar 
puncture.  This  was  first  performed  by  Corning  in 
1885.  His  aim,  however,  was  to  inject  various  drugs 
in  the  subarachnoid  space.  It  was  Wynter,  accord- 
ing to  Haynes,  who  first  proposed  the  use  of  this 
procedure  for  the  relief  of  increased  intracranial 
pressure  in  tuberculous  meningitis.  He  performed 
this  operation  upon  a  patient  in  the  comatose  stage 
of  this  disease  on  February,  1889,  twenty-two 
months  before  Quincke.  He  made  a  very  small  in- 
cision along  the  spine  of  the  second  lumbar  vertebra, 
introduced  a  Southey  tube  and  trocar  until  the 
lamina  was  reached,  then  directed  the  trocar  slightly 
downward  and  inward  through  the  ligamentum  and 
theca.  On  withdrawing  the  trocar  clear  fluid  at 
once  appeared.  By  attaching  a  fine  india-rubber 
tube  provision  for  continuous  drainage  was  made. 

The  present  technic  of  lumbar  puncture,  how- 
ever, is  based  entirely  on  the  careful  experiments  and 
explicit  directions  of  Quincke.     This  operation  was 

147 


148       MENINGOCOCCUS  MENINGITIS 

first  performed  by  him  on  December  12,  1890,  in  a 
case  of  marked  hydrocephalus  complicating  an  acute 
cerebrospinal  meningitis.  His  admirable  studies 
soon  led  to  the  general  adoption  of  this  procedure 
in  the  diagnosis  and  treatment  of  a  number  of  affec- 
tions of  the  meninges  and  central  nervous  system. 
This  minor  and  generally  harmless  operation  enables 
us  in  the  vast  majority  of  the  cases  to  make  an  exact 
etiologic  diagnosis  of  the  various  forms  of  primary 
and  secondary  meningitides.  The  omission  of  this 
procedure  (in  the  absence  of  a  post-mortem  examina- 
tion) deprives  the  report  of  any  cases  of  meningitis, 
no  matter  how  clear  it  may  be  clinically,  of  scientific 
validity. 

Anatomical  Considerations  and  Landmarks. — 
The  subarachnoid  space  is  situated  between  the 
arachnoid  membrane  and  the  pia  mater  of  the  brain 
and  spinal  cord.  At  the  lower  part  of  the  spinal  canal 
there  is  present  a  spacious  cul-de-sac,  which  surrounds 
the  spinal  nerves  forming  the  cauda  equina.  This 
space,  as  we  have  seen,  communicates  with  the  centric- 
ular  system  of  the  brain  by  means  of  the  foramen  of 
Magendie,  situated  at  the  inferior  boundary  of  the 
roof  of  the  fourth  ventricle,  and  the  two  foramina 
of  Luschka,  found  along  the  lateral  aspects  of  the 
covering  of  the  fourth  ventricle.  Up  to  the  first  year 
of  life  the  spinal  cord  extends  slightly  beyond  the 


CEREBROSPINAL  FLUID  149 

lower  level  of  the  third  lumbar  vertebra,  but,  owing 
to  the  relatively  rapid  growth  of  the  vertebra?,  it 
gradually  recedes  from  the  lower  part  of  the  lumbar 
spine  and  in  adults  does  not  reach  below  the  first 
lumbar  vertebra. 

Lusk,  in  a  series  of  fifteen  dissections,  has  very 
carefully  studied  the  relation  of  the  arachnoid  mem- 
brane to  the  posterior  surface  of  the  cord  and  the 
anatomical  features  of  the  cauda  equina.  He  found 
the  conus  medullaris  (the  terminal  portion  of  the 
cord)  at  the  level  of  the  first  lumbar  vertebra  in  11 
cases,  at  the  junction  between  the  twelfth  dorsal  and 
first  lumbar  vertebra  in  3  cases.  In  one  case  it 
reached  the  level  of  the  lower  border  of  the  second 
vertebra.  The  posterior  arachnoid  in  all  but  one  of 
the  cases  did  not  present  a  continuous  channel,  but 
was  either  adherent  to  the  posterior  surface  of  the 
cord  or  broken  up  by  transverse  septa.  The  free 
circulation  of  the  cerebrospinal  fluid  was  effected 
by  means  of  lateral  communications  with  anterior 
subarachnoid  space  over  the  concavities  of  the  liga- 
mentum  denticulatum.  In  some  of  the  cases,  in 
order  to  obtain  fluid  by  puncture  in  the  middle  line 
at  or  above  the  conus,  the  substance  of  the  cord 
would  have  had  to  be  traversed  and  the  fluid  derived 
from  the  anterior  subarachnoid  space. 

The   Nerve-roots    at   the   Cauda  Equina. — The 


150       MENINGOCOCCUS  MENINGITIS 

nerves  arise  serially  from  the  conus,  the  first  lumbar 
root  being  most  lateral,  the  lowest  sacral  occupying 
the  most  mesial  position.  A  slight  cleft  is  usual  be- 
tween the  lowest  sacral  nerves  of  each  side.  Their 
mesial  position  and  consequent  exposure  to  trauma- 
tism explain  some  of  the  cases  of  paralysis  of  the 
bladder  and  rectum  which  have  followed  lumbar 
puncture.  Delicate  adhesions  usually  bind  the  nerve- 
roots  of  the  cauda  equina  in  masses.  In  7  out  of 
15  dissections,  the  nerve-roots  were  massed  together 
against  the  anterior  subarachnoid  space.  In  some 
the  nerve-roots  were  either  distributed  peripherally 
around  the  walls  of  the  arachnoid  or  in  relation  to  its 
posterior  surface.  Adhesions  of  the  roots  to  the 
latter  were  present  in  some  of  the  dissections.  The 
retarded  flow  of  cerebrospinal  fluid  through  the 
needle,  as  is  seen  occasionally,  is  probably  due  to  the 
picking  up  of  a  nerve-root  in  the  line  of  puncture. 
This  is  best  avoided  by  a  mesial  puncture  in  the 
fourth  lumbar  space  with  a  needle  not  too  sharply 
pointed  with  the  nerve-roots  relaxed  by  sacral  ex- 
tension. The  space  below,  the  lumbosacral  space,  is 
second  in  order  of  desirability,  as  at  this  level  ad- 
hesion of  the  nerve-roots  to  the  posterior  wall  of  the 
arachnoid  sac  is  more  likely  to  occur,  and  the  sub- 
arachnoid cul-de-sac  is  shallower  at  this  level. 

The  fourth  lumbar  interspace,  the  site  of  election 


CEREBROSPINAL  FLUID  151 

for  lumbar  puncture,  is  found  at  the  level  of  a  line 
connecting  the  highest  points  of  the  iliac  crests  ( Fig. 
17).  There  are  a  number  of  anatomical  factors 
which  contribute  to  the  ease  with  which  puncture  is 


Fio.  17. — Anatomical  landmarks  for  lumbar  puncture. 

performed  in  the  lumbar  region:  first,  the  spinous 
processes  of  the  lumbar  vertebrae  are  short,  thick,  and 
widely  separated  from  one  another;  second,  the  long 
or  anteroposterior  axis  of  the  lumbar  spines  has  but 
a  slight  angular  elevation,  so  that  the  general  direc- 


152       MENINGOCOCCUS  MENINGITIS 

tion  of  the  interspinous  spaces  is  almost  at  a  right 
angle  to  the  long  axis  of  the  spine.  The  supra- 
spinous and  interspinous  ligaments  in  the  lumbar 
region  are,  however,  broad,  thick,  and  tough,  and  in 
adults  not  so  readily  penetrable  by  the  puncture 
needle. 

The  fourth  is  the  space  of  election,  as  it  is  in- 
variably below  the  level  of  the  conus,  and  there  is 
least  likelihood  of  injuring  the  nerve-roots. 

Instruments:  The  Quincke  Needle  and  Manom- 
eter (Fig.  18). — The  older  methods  of  employing 
a  syringe  needle  or  cannula  and  trocar,  with  or  without 
a  handle,  are  no  longer  in  vogue.  The  latest  model 
of  a  lumbar  puncture  set,  made  by  Beckman,  of  Kiel, 
according  to  Quincke's  directions,  consists  of  (1) 
three  needles  of  different  lengths  and  diameters,  with 
corresponding  stilettes;  (2)  a  glass  manometer  tube; 
(3)  rubber  tubing  and  coni  for  connecting  the 
needles  with  the  manometer;  (4)  a  glass  graduate 
for  collecting  and  measuring  the  cerebrospinal  fluid; 
(5)  a  cylindrical  glass  funnel  to  be  connected  with 
the  puncture  needle  with  rubber  tubing  for  the  in- 
jection of  serum.  In  order  to  secure  uniform  pres- 
sure determinations,  it  is  advisable  to  connect  the 
needle  with  the  manometer  by  means  of  a  piece  of 
catheter  tubing,  number  5,  forty  to  sixty  centimetres 
long.    Sterile  test-tubes  should  be  used  for  collecting 


CEREBROSPINAL  FLUID 


153 


and  measuring  the  fluid.  The  pressure  is  measured 
by  means  of  a  piece  of  steel  tape  graduated  in  centi- 
metres and  inches. 


Fig.  18. — a,  cannula  ;  b,  guard  ;  c,  stilette  ;  d,  conus  ;  e,  rubber  tubing, 
/,  manometer  tube.     Half  natural  size.     (After  Quincke.) 

The  needles  measure  from  four  to  ten  centimetres 
in  length  and  from  .8  to  1.6  millimetres  in  diameter. 
The  distal  extremity  of  the  needle  is  bevelled  at  an 
acute  angle  to  a  sharp  point,  forming  connection  with 
the  end  of  the  stilette  when  the  latter  is  in  situ  flush 
with  the  end  of  the  needle.     The  manometer  tube  is 


154       MENINGOCOCCUS  MENINGITIS 

fourteen  centimetres  long  and  two  and  a  half  centi- 
metres in  diameter. 

One  of  us  (Heiman)  has  had  constructed  a 
flange-like  movable  guard  for  the  needle  (Fig.  18), 
to  be  set  before  puncture  at  a  distance  from  the  point 
of  the  needle  corresponding  to  the  probable  depth  of 
insertion.  The  object  of  this  appliance  is  to  prevent 
too  deep  an  insertion  of  the  needle,  which  sometimes 
results  in  hemorrhage  from  the  venous  plexus  in  the 
anterior  wall.  The  guard  also  serves  to  steady  the 
needle  while  in  the  canal. 

Kroenig's  Apparatus. — In  cases  where  there  is 
suspicion  of  the  existence  of  a  tumor  at  the  base  of 
the  brain,  in  which  the  withdrawal  of  any  consider- 
able amount  of  fluid  might  lead  to  dangerous  symp- 
toms, it  is  advisable  to  use  the  Kroenig  instrument 
(Fig.  19).  The  calibre  of  the  measuring  tube  is  so 
small  that  a  few  drops  of  fluid  are  sufficient  to  fill  it. 
If  the  column  of  fluid  does  not  show  any  oscillation, 
it  is  an  indication  that  there  is  compression  of  the 
structures  at  the  base  of  the  brain,  and  further  with- 
drawal of  fluid  must  be  discontinued. 

Crohn  has  devised  a  useful  apparatus  which  per- 
mits of  the  withdrawal  of  a  minimum  amount  of 
fluid  for  the  registration  of  the  pressure  in  the  sub- 
arachnoid space.  The  apparatus  consists  of  the  parts 
shown  in  Fig.  20.     It  presents  the  advantages  that 


CEREBROSPINAL  FLUID 


155 


there  is  no  opportunity  for  the 
accidental  escape  of  fluid  and  the 
registering  apparatus  is  small  and 
graduated. 

Preparation  and  Position  of 
the  Patient  and  Operator. — We 
almost  invariably  puncture  in  the 
horizontal  position.  In  the  event 
of  an  apparently  dry  tap,  it  may 
very  occasionally  be  desirable  to  in- 
crease the  pressure  of  the  cerebro- 
spinal fluid  by  placing  the  patient 
in  the  sitting  posture.  It  has  been 
claimed  that  in  this  posture  sedi- 
mentation of  cerebrospinal  exudate 
occurs,  thus  facilitating  the  search 
for  abnormal  elements.  This  ad- 
vantage   i  s 

largely  ' 

a  theoretical 

one,  and  is  more  than  counter 
balanced  by  the  added  danger 
of   collapse   during   the   performance 
of  the  puncture  and  the  greater  diffi- 
culty   in    technic    encountered    when 
puncture  is  done  in  a  sitting  posture. 


Fia.  20.— Crohn's 
apparatus  for  estima- 
tion of  pressure  in  the 


mi  ■•         .       •  i  T  ,i  in,        iion  oi  pressure  in  int 

1  he      patient      IS      placed      On      the      left       cerebrospinal  system 


156       MENINGOCOCCUS  MENINGITIS 

side  close  to  the  edge  of  the  operating  table  or 
bed.  One  assistant  faces  the  patient  and  flexes  the 
spine  by  grasping  with  his  right  hand  the  nape  of 
the  neck  and  with  his  left  hand  the  legs.  This  posi- 
tion prevents  struggling  of  the  patient,  brings  into 
prominence  the  lumbar  spines,  and  increases  the 
elastic  pressure  of  the  spinal  fluid.  A  second  assist- 
ant, during  the  time  that  the  operator  is  disinfecting 
his  hands,  renders  surgically  aseptic  the  skin  at  the 
site  and  vicinity  of  the  puncture.  Recently  we  have 
applied  tincture  of  iodine  on  the  dry  skin  for  steriliza- 
tion of  the  field  of  operation,  with  very  satisfactory 
results.  At  the  edge  of  the  table  or  bed  and  on  the 
floor  are  spread  wet  bichloride  towels,  and  sterile 
towels  are  arranged  about  the  field  of  operation.  An 
anaesthetic  is  usually  not  required.  The  needle, 
manometer,  tubing  with  the  attached  conus,  and  the 
measuring  tape  are  sterilized  by  boiling. 

Method  of  Procedure. — The  operator  locates  the 
desired  space  and  steadies  the  vertebra  above  by 
placing  the  thumb  and  middle  finger  of  the  left  hand 
on  the  laminae,  and  the  index  finger  on  the  spinous 
process  (Fig.  21).  Grasping  the  needle  and  enclosed 
stilette  in  the  right  hand,  and  placing  the  index  finger 
on  the  needle  at  the  level  at  which  it  is  assumed  the 
needle  will  penetrate  (i.e.,  from  two  to  five  centi- 
metres, according  to  the  age),  it  is  plunged  in  the 


Processus  spinosus 

Plexus  venosus  vertebralis 
posterior 
Rete  venosum  vertebrae 
/ 


Processus 
-articularis  superior 


V.  intervertebralis 


Processus 
transversus 


^^  Plexus  venosi  vertebrales 
interni 


V.  basivertebralis 


Corpus 
vertebrae 


Plexus  venosus 
vertebralis  anterior 


Fig.  23. 


-Spinal  veins  in  a  horizontal  section  viewed  from  above.     Only  the  body  of 
the  vertebra  has  been  cut  through  .    (Spalteholz.) 


CEREBROSPINAL  FLUID 


157 


middle  line  of  the  space  and  along  the  upper  border 
of  the  lower  spinous  process  (so  as  to  avoid  the 
tubercle  on  the  posterior  extremity  of  the  inferior 
surface  of  the  spinous  process),  in  a  direction  almost 
horizontal  and  at  an  inferior  (caudad)  angle  of  10° 
to  the  axis  of  the  spine  (Fig.  22). 
By  directing  the  needle  in  this 
manner,  it  can  be  inserted  to  a 
deeper  level  without  encountering 
the  anterior  venous  plexus  of  the 
vertebral  column  ( Fig.  23 ) .  Inex- 
perienced operators  often  make 
the  blunder  of  pushing  the  needle 
directly  forward,  and  thus  fre- 
quently obtain  bloody  fluid.  This 
untoward  result,  while  not  usually 
dangerous  to  the  patient,  often 
renders  it  impossible  for  us  to 
judge  of  the  macroscopic  appear- 
ance of  the  fluid.  In  the  absence 
of  the  important  data  yielded  by 
the  gross  appearance  of  the  fluid, 
it  may  be  very  difficult  to  decide  whether  to  inject 
serum  at  once  or  not.  The  stilette  is  now  withdrawn 
and  the  conus  at  once  inserted  into  the  hilt  of  the 
needle,  thus  connecting  the  latter  with  the  manom- 
eter by  means  of  the  rubber  tubing.     The  horizontal 


Fig.    22. — Showing  direc- 
tion of  needle. 


158       MENINGOCOCCUS  MENINGITIS 

arm  of  the  manometer  tube  is  held  about  three  centi- 
metres below  the  level  of  the  needle  until  the  cerebro- 
spinal fluid  appears  in  the  manometer.  The  horizontal 
arm  of  the  instrument  is  then  raised  to  the  level  of 
the  needle  and  the  height  of  the  column  of  fluid  in  the 
manometer  is  read  ofT  on  the  tape,  its  zero  mark  hav- 
ing been  placed  at  the  level  of  the  site  of  puncture 
( Fig.  24 ) .  The  manometer  is  again  lowered  and  the 
desired  amount  of  fluid  allowed  to  escape  into  sterile 
tubes.  From  time  to  time  the  pressure  should  be 
read  by  raising  the  tube,  so  as  to  prevent  the  produc- 
tion of  a  subnormal  pressure  in  the  subarachnoid 
space.  The  evacuation  of  the  fluid  should  proceed 
slowly.  The  rate  of  flow  is  regulated  by  raising  or 
lowering  the  manometer.  If  the  flow  is  very  slow 
because  of  low  hydrostatic  pressure,  it  may  at  times 
be  artificially  increased  by  more  forcible  flexion  of 
the  spine  (elastic  pressure)  or  by  making  the  patient 
cough,  cry,  or  breathe  deeply,  or  by  compressing  the 
patient's  abdomen   (vascular  pressure). 

The  use  of  the  manometer  as  a  routine  is  advis- 
able, because  the  pressure  constitutes  the  best  guide  in 
deciding  how  much  fluid  it  is  safe  to  withdraw  (Figs. 
25  and  26).  It  is  probable  that  some  of  the  reported 
fatalities  have  occurred  as  a  result  of  too  free  or  too 
rapid  evacuation  of  the  fluid.     This  can  be  avoided 


Fig    25      Estimation  of  pressure  of  cerebrospinal  flui<l  by  means  of  Quincke's  manometer. 


I  10    26      Introduction  of  antimeningitie  Mrum  into  the  spinal  canal,  by  means  of  funnel 


CEREBROSPINAL  FLUID 


159 


if  the  pressure  is  carefully  observed  at  frequent  inter- 
vals and  never  allowed  to  fall  much  below  normal. 
If  the  fluid  does  not  appear  immediately  upon  the 


*>ec3rejr/f/3. 


Fia.  24. — Measuring  the  pressure.     (After  Quincke.) 

withdrawal  of  the  stilette,  it  should  not  be  concluded 
that  there  is  a  "  dry  tap,"  before  waiting  the  reason- 
able period  and  trying  the  artificial   means   of  in- 


160       MENINGOCOCCUS  MENINGITIS 

creasing  pressure.  If  these  attempts  are  unsuccess- 
ful, the  needle  should  be  left  in  situ  and  another 
needle  inserted  in  the  space  above.  A  small  quantity 
of  sterile  salt  solution  is  then  allowed  to  flow  through 
the  upper  needle,  and  if  it  escapes  from  the  lower 
needle  we  may  be  certain  that  both  needles  are  in 
the  subdural  space.  Only  when  this  procedure  has 
been  carried  out  are  we  justified  in  speaking  of  "  dry 
tap."  This  is  usually  due  to  obliteration  or  valvular 
closure  of  the  foramina  of  Magendie  or  Luschka  or 
the  aqueduct  of  Sylvius.  In  some  cases  so-called 
"  dry  taps  "  are  due  to  pushing  forward  instead  of 
penetration  of  the  dura  by  the  point  of  the  needle, 
picking  up  of  nerve-roots,  or  occlusion  of  the  lumen 
by  tissue,  fibrin,  or  pus.  Such  occlusion  is  usually 
readily  overcome  by  reinserting  the  stilette. 

It  is  of  the  greatest  importance  that  the  patient 
be  watched,  either  by  the  operator  or  a  competent 
medical  assistant,  for  at  least  a  period  of  fifteen  to 
twenty  minutes  after  the  performance  of  a  puncture. 
Occasionally  sudden  cessation  of  respiration  (apnoea) 
takes  place  during  this  period,  and,  unless  artificial 
respiration  is  resorted  to  immediately  on  its  occur- 
rence, a  fatal  result  may  take  place. 

Physiology. — The  secretion  of  cerebrospinal  fluid 
is  chiefly  effected  through  the  agency  of  the  various 
choroid  plexuses.     It  is  not  unlikely  that  the  blood- 


CEREBROSPINAL  FLUID  161 

vessels  of  the  meninges  also  play  a  part  in  its  produc- 
tion. In  addition  to  its  serving  as  a  lubricating  fluid, 
the  cerebrospinal  fluid  maintains  the  intracranial 
pressure,  which  tends  to  vary  with  cardiac  action, 
respiratory  rhythm,  and  changes  in  the  position  of 
the  body,  at  a  constant  level.  The  pressure  in  the 
subarachnoid  space  is  always  a  few  millimetres  of 
mercury  above  the  cerebral  venous  pressure.  To  this 
is  due  the  flow  of  fluid  from  the  subarachnoid  space 
into  the  venous  system.  As  the  specific  gravity  of  the 
blood  is  greater  than  that  of  the  cerebrospinal  fluid, 
the  osmotic  exchange  is  in  the  same  direction.  The 
intracranial  pressure,  as  well  as  the  pressure  in  the 
subarachnoid  space  in  the  adult  and  older  child,  is 
maintained  at  a  fairly  constant  level  through  the 
agency  of  the  Pacchionian  bodies.  With  the  systolic- 
expansion  of  the  arteries  at  the  base  of  the  brain,  the 
Pacchionian  bodies  and  the  cerebral  veins  are  com- 
pressed and  emptied  of  the  cerebrospinal  fluid 
present  in  them,  which  flows  through  the  thin  layer 
of  the  dura  into  the  sinuses.  During  the  diastolic 
period  the  Pacchionian  bodies  expand  and  aspirate 
the  cerebrospinal  fluid  from  the  subdural  and  sub- 
arachnoid spaces. 

In    infancy    the    functions    of    the    rudimentary 
Pacchionian  bodies  are  performed  by  the  fontanelles, 
11 


162       MENINGOCOCCUS  MENINGITIS 

which  by  their  alternate  expansion  and  retraction 
maintain  the  intracranial  pressure  at  a  normal  level. 

By  injecting  ink  into  the  subarachnoid  spaces  of 
animals  and  following  the  movements  of  the  particles, 
Sicard  has  been  able  to  demonstrate  the  existence  of  a 
circulation  in  the  cerebrospinal  fluid.  Within  from 
two  to  four  hours  of  the  injection  of  the  ink  in  the 
lumbar  region,  the  particles  had  reached  the  occipito- 
atloid  region.  Somewhat  later  the  base  of  the  brain 
in  the  region  between  the  peduncles  and,  still  later, 
the  lateral  ventricles  were  reached.  No  ink  was 
present  in  the  cerebral  cortex  before  ten  to  twelve 
hours.  Injected  in  the  occipito-atloid  region  the  base 
of  the  brain  was  reached  in  one-half  to  one  hour,  then 
the  lateral  ventricles  and  lumbar  region.  The  cere- 
bral cortex  was  attained  at  a  much  later  period.  In- 
jected within  the  cranial  arachnoid,  the  particles  of 
ink  remained  in  situ  for  ten  to  twelve  hours.  He 
found  that  substances  in  solution  in  the  cerebrospinal 
fluid  were  removed  by  osmosis,  while  solid  particles 
in  suspension  were  removed  by  leucocytic  diapedesis. 

Characteristics  of  Normal  Cerebrospinal  Fluid. — 
It  is  a  perfectly  clear  and  limpid  fluid  resembling 
spring  water.  The  amount  varies  with  age  and  sex, 
and  does  not  usually  exceed  60  to  80  cubic  centi- 
metres (Howell)  in  the  normal  adult.  It  possesses 
few  cellular  elements,  usually  not  more  than  two  to 


CEREBROSPINAL  FLUID  163 

seven  cells  per  cubic  millimetre.  Polymorphonuclear 
cells  are  never  present  in  normal  cerebrospinal  fluid. 
According  to  Peyton-Rous,  the  average  protein  con- 
tent is  0.3  gram  per  litre,  but  it  may  vary  from  %  to 
Y%  of  a  gram.  The  normal  pressure  in  the  sub- 
arachnoid space  is  estimated  variously  by  different 
observers.  Quincke  gives  it  at  30  to  50  millimetres 
of  water.  Kronig  finds  it  to  vary  from  120  to  180 
millimetres,  whereas  Peyton-Rous  found  variations 
from  70  to  300  millimetres.  It  is  altered  by  cough- 
ing, straining,  fright,  and  change  in  the  position  of 
the  patient.  It  rarely  coagulates  spontaneously.  It 
possesses  no  toxic  properties,  but  in  vitro  it  is 
bactericidal. 

Cerebrosjrinal  Fuid  in  Meningococcus  Menin- 
gitis.— The  fluid  shows  great  variations  according  to 
the  type  and  stage  of  the  disease.  The  rate  of  flow 
is  far  from  uniform.  At  times  it  flows  drop  by  drop ; 
at  other  times  it  runs  freely  in  a  continuous  stream. 
There  is  likewise  marked  variation  in  pressure.  The 
lowest  pressure  we  have  seen  was  40  millimetres 
(about  normal)  in  an  infant  seventeen  months  old; 
the  highest  510  millimetres  in  a  child  seven  years  of 
age.  In  the  acute  stage,  with  proper  technic  it  is 
usually  possible  to  remove  a  quantity  of  fluid  suffi- 
cient for  examination.  Not  infrequently  we  have 
succeeded   in  obtaining  from  thirty  to   forty  cubic 


164       MENINGOCOCCUS  MENINGITIS 

centimetres  of  fluid.  In  the  chronic  stage,  and 
particularly  in  cases  of  the  posterior  basic  type,  "  dry 
taps  "  are  relatively  frequent. 

Macroscopic  Appearances. — At  the  height  of  the 
disease  the  fluid  is  usually  grayish-yellow,  turbid,  or 
purulent;  at  times  it  is  so  thick  that  it  does  not  flow 
with  ease  through  the  needle.  In  the  first  twenty- 
four  hours  it  is  frequently  clear  or  only  slightly 
opalescent.  On  standing  in  the  case  of  a  purulent 
fluid  a  yellowish,  homogenous  and  viscid  deposit 
collects  at  the  bottom  of  the  tube,  while  the  super- 
natant fluid  becomes  somewhat  clarified.  A  fibrin 
reticulum  is  occasionally  seen  floating  in  the  fluid  or 
adherent  to  the  tube.  Along  the  sides  of  the  tube  a 
deposit  of  fine  yellow  flakes  resembling  sulphur 
particles  may  form.  As  a  rule,  no  prognostic  data 
are  derivable  from  the  degree  of  turbidity  or 
purulence. 

Microscopic  Appearance. — It  is  usually  necessary 
to  centrifugalize  the  fluid.  The  predominant  cell  at 
this  stage  of  the  disease  is  the  polymorphonuclear.  It 
is  usually  present  in  the  proportion  of  80  to  100  per 
cent,  of  the  total  cell  contents.  It  rarely  gives  the 
appearance  of  the  normal  polymorphonuclear  cell  of 
the  blood.  Usually  its  borders  lack  sharpness  and  the 
protoplasm  is  homogeneous,  non-granular,  and 
vacuolated.     The  chromatin  network  of  the  nucleus 


CEREBROSPINAL  FLUID  165 

is  not  sharply  stained.  At  times  the  nucleus  dis- 
appears. Some  of  the  cells  are  so  markedly  de- 
generated that  only  a  cellular  debris  remains.  The 
lymphocytes  are  usually  present  in  the  proportion  of 
10  to  15  per  cent.  As  a  rule,  they  show  less  degenera- 
tion than  the  polymorphonuclears.  In  addition  to 
these  cells  there  are  present  a  variable  number  of 
large  mononuclear  cells.  They  possess  homogenous 
protoplasm  and  a  poorly  staining  reniform  or 
rounded  nucleus.  Frequently  there  are  vacuoles 
present  which  contain  one  or  more  ingested  cells. 
These  large  cells,  as  we  have  seen,  are  derived  from 
the  connective  tissue  and  adventitia  of  the  blood- 
vessels of  the  meninges. 

In  the  early  stages  the  meningococcus  is  present 
in  considerable  abundance  in  the  cerebrospinal  fluid. 
At  times,  even  when  few  pus-cells  are  present, 
hundreds  of  micro-organisms  may  be  seen  in  a  micro- 
scopic field.  The  relative  proportion  of  extra-  and 
intracellular  organisms  varies  greatly.  As  we  shall 
see  later,  soon  after  the  injection  of  anti-meningo- 
coccic  serum,  the  greater  number  of  extracellular 
organisms  disappears  from  the  fluid.  It  is  important 
to  remember  that  occasionally  great  difficulty  is  en- 
countered in  demonstrating  microscopically  or  cultur- 
ally the  presence  of  the  meningococcus,  even  when  the 
fluid  shows  marked  turbidity  and  the  cellular  elements 


166       MENINGOCOCCUS  MENINGITIS 

are  present  in  great  abundance.  In  these  cases,  as 
will  be  seen  later,  the  precipito  reaction  of  Vincent 
and  Bellot  may  prove  invaluable  as  a  diagnostic  aid. 
It  is  needless  to  add  that  the  Gram  stain  must 
always  be  employed.  Only  Gram-negative  diplo- 
cocci  having  the  characteristic  morphology  and 
grouping  of  the  meningococcus  are  to  be  considered 
as  meningococci.  Where  a  laboratory  is  available, 
cultivation  of  the  organism  and  subsequent  submis- 
sion to  fermentation  and  agglutination  tests  are 
desirable. 

Chemical  Characters. — In  addition  to  the  more 
important  cytological  and  bacteriological  changes 
present  in  the  acute  stage  of  meningococcus  menin- 
gitis, there  are  seen  a  number  of  alterations  in  the 
chemical  characters  of  the  cerebrospinal  fluid.  Albu- 
min, determined  either  by  the  heat  or  nitric  acid  test, 
is  increased  in  quantity,  being  in  the  proportion  of 
2  to  3  grams  per  litre.  Sugar  is  usually  decreased, 
but  this  is  not  a  constant  feature.  It  is  often  asserted 
that  the  absence  of  sugar  from  the  cerebrospinal  fluid 
is  an  important  differential  characteristic  between 
this  form  of  meningitis  and  tuberculous  meningitis. 
This  assertion  is  not  borne  out  by  our  personal 
observations,  for  we  have  not  infrequently  seen  an 
apparently  normal  quantity  of  sugar  in  the  cerebro- 
spinal fluid  of  meningococcus  meningitis.     Similar 


CEREBROSPINAL  FLUID  167 

observations  on  the  inconstancy  of  this  feature  are 
recorded  by  Sophian.  The  chlorides  are  somewhat 
diminished.  Cryoscopy  usually  shows  a  lowering  of 
a,  but  there  is  no  uniformity  in  the  results  obtained 
by  those  who  have  studied  this  physical  property  of 
the  fluid.  Kopetzky  found  a  decrease  in  alkalinity 
due  to  the  presence  of  combined  acid.  This  observer 
was  also  able  to  demonstrate  the  presence  of  lactic 
acid. 

Changes  in  the  Cerebrospinal  Fluid  in  the  Course 
of  the  Disease. — According  to  Netter,  who  has  made 
a  number  of  important  contributions  on  this  phase  of 
the  subject,  the  cerebrospinal  fluid  in  seventy-five  per 
cent,  of  the  cases  during  the  first  twenty  hours  of  the 
disease  is  clear  or  slightly  opalescent,  rich  in  albumin 
and  poor  in  cells,  and  contains  an  abundant  number 
of  meningococci.  In  an  infant  6  weeks  of  age  we 
have  seen  a  perfectly  clear  fluid  under  slightly  in- 
creased pressure,  free  from  meningococci  on  the  third 
day  of  the  disease.  Two  days  later,  on  the  day  pre- 
ceding death,  the  fluid  was  slightly  turbid  and  yielded 
a  moderate  number  of  meningococci.  Too  much 
stress  can  not  be  laid  on  the  fact,  not  always  clearly 
recognized,  that  the  presence  of  clear  fluid  does  not 
necessarily  exclude  the  existence  of  meningococcic 
infection  of  the  meninges. 

With    the    subsidence    of    acute    symptoms    the 


168       MENINGOCOCCUS  MENINGITIS 

number  of  cellular  elements  gradually  diminishes  and 
the  relative  proportions  of  the  various  cells  described 
above  undergo  important  changes.  With  the  diminu- 
tion in  the  number  of  cells,  the  cerebrospinal  fluid 
becomes  less  and  less  turbid.  The  polymorphonu- 
clears and  large  mononuclears  gradually  disappear, 
while  the  relative  number  of  lymphocytes  becomes 
increased.  At  this  stage  of  the  disease  the  cytologic 
character  of  the  fluid  is  not  unlike  that  usually  seen 
in  tuberculous  meningitis.  Even  at  an  advanced 
stage  of  convalescence,  eight  to  ten  days  after  com- 
plete disappearance  of  all  acute  symptoms,  the 
cerebrospinal  fluid  may  show  a  considerable  number 
of  lymphocytes.  It  has  not  been  definitely  deter- 
mined when  the  fluid  finally  assumes  all  its  normal 
characteristics.  The  disappearance  of  the  meningo- 
coccus from  the  fluid  is  even  more  rapid  than  that 
of  the  polymorphonuclears.  The  free  organisms 
usually  disappear  first.  At  the  end  of  the  first  week 
the  search  for  the  meningococcus  is  quite  often  fruit- 
less. Even  if  a  few  organisms  are  microscopically 
demonstrable,  their  viability  has  suffered  to  such  a 
degree  that  cultivation  on  suitable  artificial  media 
is  rarely  crowned  with  success. 

The  orderly  progression  of  the  changes  above 
described  is,  however,  subject  to  unaccountable  varia- 
tions. From  time  to  time,  often  in  the  absence  of 
any  change  in  the  clinical  symptoms,  a  fluid  is  with- 


CEREBROSPINAL  FLUID  169 

drawn  differing  markedly  in  character  from  the  fluid 
obtained  by  the  immediately  preceding  puncture.  It 
may  be  very  turbid,  though  previously  quite  clear. 
The  number  of  polymorphonuclears  may  show  a 
sudden  marked  increase.  In  other  cases  the  menin- 
gococci become  greatly  increased  in  number.  The 
explanation  for  these  sudden  changes  is  not  quite 
clear.  In  the  absence  of  clinical  evidence  of  an  ex- 
acerbation, they  can  hardly  be  attributed  to  a  relight- 
ing of  the  infectious  process.  The  most  probable 
explanation  is  that  in  these  cases  the  spinal  sub- 
arachnoid space,  as  a  result  of  the  removal  of  an 
obstruction  at  some  point,  becomes  suddenly  flushed 
with  exudate  coming  from  the  ventricles  and  base 
of  the  brain.  It  can  readily  be  seen  how  important 
it  is  to  follow  the  changes  in  the  cerebrospinal  fluid 
by  lumbar  puncture  at  frequent  intervals,  until  there 
is  definite  evidence  of  absorption  of  the  entire 
exudate. 

As  we  shall  see  later,  the  rapidity  of  the  regressive 
changes  in  the  cerebrospinal  fluid  is  much  greater 
when  antimeningococcic  serum  is  introduced  in  the 
subarachnoid  space.  The  extracellular  organisms  be- 
come greatly  diminished  or  disappear  entirely  after 
the  first  injection.  Meningococci  are  rarely  found 
after  the  third  injection.  The  cellular  elements  like- 
wise show  a  rapid  decrease  in  number  and  the  fluid  be- 
comes clear  in  a  much  shorter  time. 


170       MENINGOCOCCUS  MENINGITIS 

THE  CHARACTER  OF  THE  CEREBROSPINAL  FLUID  IN  THE 
VARIOUS  TYPES  OF  MENINGOCOCCUS    MENINGITIS 

Fulminating  Type. — The  appearance  and  char- 
acters of  the  cerebrospinal  fluid  in  this  type  of  menin- 
gitis are  not  uniform.  Most  commonly,  on  account  of 
the  rapidity  of  the  intoxication  and  the  lack  of  time 
for  the  development  of  severe  inflammatory  changes, 
the  fluid  withdrawn  is  clear  and  contains  an  increased 
amount  of  albumin,  few  cellular  elements,  and  a 
variable  number  of  organisms.  The  predominant 
cell,  unlike  that  found  in  the  ordinary  type  of  menin- 
gitis, is  the  lymphocyte. 

In  some  cases  which  are  not  truly  fulminating  in 
type,  as  a  careful  anamnesis  reveals  the  presence  for 
several  days  of  a  number  of  prodromal  symptoms,  the 
cerebrospinal  fluid  shows  the  usual  appearance  and 
cytological  characteristics  of  the  fluid  in  the  ordinary 
acute  type  of  this  disease. 

In  other  cases  the  fluid  is  practically  sterile  and 
normal  in  appearance.  Without  a  careful  micro- 
scopic examination  of  the  meninges,  it  is  often  diffi- 
cult in  these  cases  to  say  whether  a  true  meningitis 
is  present  or  a  fulminating  form  of  meningococcsemia. 

Mild  Type. — The  fluid  is  usually  clear,  albumin- 
ous, and  contains  a  variable  number  of  cells  and 
organisms.    In  other  cases  the  fluid  is  turbid  and  does 


CEREBROSPINAL  FLUID  171 

not  differ  from  that  present  in  more  severe  types  of 
the  disease. 

Abortive  Types. — In  these  eases  the  cerebro- 
spinal fluid  is  usually  clear  and  shows  only  slight  in- 
crease in  albumin  and  cells.  The  meningococcus  is 
only  rarely  discoverable.  In  other  cases  the  fluid 
shows  no  departure  from  the  normal.  The  diag- 
nosis must  be  based  on  the  clinical  course  of  the 
disease  rather  than  the  character  of  the  cerebrospinal 
fluid. 

Chronic  Types. — At  times,  especially  in  the  cases 
belonging  to  the  posterior  basic  type,  it  is  difficult  to 
evacuate  fluid  from  the  spinal  subarachnoid  space. 
Several  causes  separately  or  in  combination  may  con- 
tribute to  this  result.  It  is  usually  assumed  that 
obliteration  of  the  foramen  of  Magendie  is  the  cause 
most  frequently  present.  In  other  cases  adhesions 
in  the  vicinity  of  the  cerebellum  and  pons  obliterate 
the  communication  between  the  cerebral  and  spinal 
subarachnoid  spaces.  In  others  it  must  be  assumed 
that  the  obstruction  is  valvular  rather  than  organic 
in  nature. 

The  fluid  is  usually  clear  and  slightly  yellow  or 
grayish  in  color.  The  few  cells  present  are  composed 
almost  exclusively  of  small  lymphocytes.  The  menin- 
gococcus is  often  absent,  or  present  in  such  small 
numbers   that   prolonged   microscopic   search    is   re- 


172       MENINGOCOCCUS  MENINGITIS 

quired.  Successful  growth  on  artificial  media  is 
rarely  attainable.  In  these  cases  intraventricular 
puncture  may  evacuate  a  fluid  differing  markedly 
from  that  yielded  by  lumbar  puncture.  Long  after  it 
has  disappeared  from  the  spinal  fluid,  the  meningo- 
coccus may  be  found  in  the  ventricular  exudate. 

Bibliography 

Corning:   New  York  Med.  Jour.,  1885,  xlii,  483. 

Wynter:  Lancet,  1891,  i,  981. 

Quincke:   Verhand.  d.  Cong.  f.  Inner  Med.,  1891,  x,  321. 

Berl.  klin.  Wochenschr.,  1891,  xxviii,  929. 
Sicard:   Les  Injections  Sous-arachnoid,  Paris  These,  1899- 

1900. 
Quincke:     Die    Technik    der   Lumbalpunktion,    Berlin    and 

Vienna,  1902. 
Heiman:  New  York  Med.  Jour.,  1906,  xxxiv,  975. 
Nonne  and  Apelt:    Neurol  Centralb.,  1908,  xxvii,  181. 
Netter:  Soc  de  Biol.,  1910. 

Bybee  and  Lorenz:   Arch.  Int.  Med.,  1911,  vii,  38. 
Lusk:    Annals  Surgery,  1911,  liv,  449. 
Weil  and  Kofka:   Med.  Klinik,  1911,  vii,  1314. 
Crohn:   Jour.  Amer.  Med.  Assn.,  1911,  lvi,  962. 
Reichmann:    Deut.  Zeit.  f.  Nervenhk.,  1911,  xlii,  i. 
Bruynoghe:  Cent.  J.  Bakt.,  1911,  ix,  1  Abt.  Orig.,  581. 
Haynes:    Trans.  Amer.  Laryng.  Rhinolog.  Soc,  1912,  186. 
Kopetsky :    Trans.  Amer.  Laryng.  Rhinolog.  Soc,  1912,  118. 
Braun  and  Husler:    Deut.  med.  Wochenschr.,  1912,  xxxviii, 

1179. 
v.  Gryse:    Compt.  rend.  Soc.  de  Biol.,  1912,  lxxii,  369. 


CHAPTER  X 

Complications  and  Sequels  of  Meningococcus 
Meningitis 

Owing  to  the  great  variations  exhibited  by  the 
clinical  picture  of  the  disease  in  different  epidemics, 
it  is  rather  difficult  to  draw  the  dividing  line  between 
those  symptoms  which  constitute  an  integral  part  of 
the  disease  and  those  which  may  properly  be  called 
complications.  The  number  and  severity  of  the 
latter  vary  markedly  in  individual  epidemics.  In- 
volvement of  the  eyes,  ears,  lungs,  or  joints  may  be 
seen  in  a  considerable  proportion  of  the  cases  in  one 
epidemic  and  but  rarely  in  another.  Moreover,  there 
may  be  great  variations  in  the  frequency  of  certain 
complications  at  different  stages  of  the  same  epi- 
demic. One  of  the  most  frequent  and  important  com- 
plications, which  is  practically  always  present  in  the 
protracted  forms  of  the  disease,  is  hydrocephalus. 
On  account  of  its  importance  from  the  stand-point 
of  immediate  and  ultimate  prognosis,  both  as  regards 
life  and  the  mental  condition  of  the  patient,  it  will 
receive  extended  treatment  in  another  chapter.  Here 
we  shall  discuss  a  number  of  complications  involving 
the  nervous  system,  special  senses,  and  viscera. 

173 


174       MENINGOCOCCUS  MENINGITIS 

NERVOUS  COMPLICATIONS 

These  may  be  divided  into  psychic,  motor,  and 
sensory. 

Psychic. — While  the  delirium  usually  seen  at  the 
height  of  the  disease  is  ordinarily  of  a  mild  character, 
it  occasionally  becomes  so  violent  that  restraint  by 
a  straight- jacket  is  demanded.  Occasionally  the 
patients  suffer  for  days  at  a  time  from  hallucinations 
and  delusions.  In  the  fulminating  and  hyperacute 
types,  deep  coma  may  be  present  throughout  the 
whole  stormy  course  of  the  disease.  In  one  case  that 
made  a  complete  recovery,  a  cataleptic  state  of 
several  weeks'  duration  was  observed  during  the 
height  of  the  disease  (Fig.  27). 

Motor. — These  have  varied  greatly  both  in  fre- 
quency and  severity  in  different  epidemics.  While 
cranial-nerve  paralyses  are  comparatively  frequent, 
those  of  the  spinal  nerves  are  rarely  encountered.  As 
we  have  seen,  disturbances  of  the  extrinsic  muscles 
of  the  eye,  manifested  in  various  forms  of  strabismus 
and  deviations,  are  quite  frequently  present  at  one 
stage  or  another  of  the  disease.  The  opinion  as  to 
the  frequency  and  permanence  of  paralysis  of  the 
extremities  in  this  disease  has  undergone  great 
changes  from  time  to  time.  The  observers  of  the 
early  period  of  the  clinical  recognition  of  the  disease, 


.  1 1 


FlO.  27.— Catalepsy  complicating  cerebrospinal  menintriris,  am-  six  years 


COMPLICATIONS  AND  SEQUELAE      175 

such  as  Tourdes,  Hirsch,  Niemeyer,  and  Leyden, 
considered  paralysis  of  the  extremities  a  rare  com- 
plication. Subsequent  to  this  period  a  comparatively 
large  number  of  cases  showing  this  complication  was 
reported  in  the  literature.  This  was  probably  due  to 
confusion  of  this  disease  with  acute  anterior  polio- 
myelitis, in  which,  as  we  know,  early  symptoms  of 
meningeal  irritation  are  at  times  quite  common. 
Since  the  advent  of  lumbar  puncture,  which  permits 
the  making  of  an  accurate  differential  diagnosis  be- 
tween the  two  diseases,  the  pendulum  of  medical 
opinion  has  swung  back  to  the  earlier  view  that  this 
complication  is  rare.  The  infrequency  of  paralysis 
of  the  limbs  is  seen  from  the  following  statistics, 
quoted  from  Netter  and  Debre. 

Tourdes  (1843)  saw  among  196  cases  one  case  of 
preagonal  hemiplegia;  one  hemiplegia  accompanied 
by  pain,  cured;  and  monoplegia  in  a  fatal  case. 

Niemeyer  (1865)  saw  in  126  cases  only  one  hemi- 
plegia in  a  fatal  case. 

Councilman,  Mallory  and  Wright  (1898)  saw 
in  111  cases  two  hemiplegias,  cured;  one  monoplegia 
of  the  leg,  cured. 

Goeppert  (1904)  saw  in  300  cases  four  hemi- 
plegias;  one   paraplegia,   cured. 

Netter  (before  the  use  of  serum)  in  33  cases  saw 
one    hemiplegia;    one    spinal-root    paralysis,    cured. 


176       MENINGOCOCCUS  MENINGITIS 

In  100  cases  (since  the  use  of  serum)  he  had  2  spinal- 
root  paralyses,  cured. 

Hemiplegia  is  the  most  frequent  form  of  this 
paralysis.  It  is  occasionally  seen  in  severe  cases 
shortly  before  death.  Usually,  though  the  muscles 
show  some  degree  of  weakness  and  the  gait  is  un- 
steady, the  reflexes  remain  normal.  The  paralysis 
lasts  from  a  few  days  to  several  weeks.  Complete 
recovery  is  the  rule.  Incurable  cases  of  hemiplegia, 
showing  exaggeration  of  the  deep  reflexes  and  at 
the  later  stage  muscular  contractures,  are  extremely 
rare. 

Flaccid  paralysis  of  a  number  or  of  all  of  the 
muscles  of  one  extremity  is  still  more  rare.  Being 
radicular  or  neuritic  in  origin,  pain  or  tenderness 
along  the  course  of  the  affected  nerve  is  a  frequent 
accompaniment  of  this  form  of  paralysis.  As  might 
be  expected,  loss  of  deep  reflexes,  change  in  electrical 
reaction  (at  times  reaction  of  degeneration),  and 
muscular  atrophy  are  usually  present.  Though  the 
paralysis  may  persist  for  months,  ultimate  recovery 
almost  always  results.  Authentic  cases  of  permanent 
flaccid  paralysis,  due  to  destruction  of  the  motor 
ganglion- cells  of  the  anterior  horn,  are  extremely 
rare.  Many  of  the  cases  reported  in  the  literature 
probably  belong  to  the  meningeal  type  of  anterior 
poliomyelitis. 


COMPLICATIONS  AND  SEQUELS      177 

Cerebrospinal  Meningitis  (Epidemic). — M.  W.,  age 
3^2  years ;  admitted  Ma}-  13, 1911 :  discharged,  well,  June  22, 
1911. 

Family  History. — Negative. 

Past  History. — Full  term;  normal  delivery.  Tonsillitis; 
bronchitis;  diphtheria  1^2  years  ago;  no  exanthemata. 

Present  Illness. — May  12,  after  supper  child  was  noticed 
to  be  somnolent,  but  did  not  have  any  definite  complaint.  This 
morning  had  frequent  generalized  convulsions,  between  which 
child  was  stuporous.  Vomited  spontaneously  several  times. 
High  fever  all  day. 

Examination. — General  condition  good;  well  nourished. 
Alternately  irritable  and  talkative.  Stuporous.  Active 
delirium   at  times. 

Eyes  :  React  to  light ;  weakness  of  right  external  rectus  ; 
does  not  seem  to  see. 

Head :     No  rigidity ;  Macewen  present ;  no  facial. 

Mouth:     Tonsils  much  enlarged  and  reddened. 

Extremities  :  During  period  of  stupor  are  flaccid.  Knee- 
jerk  obtained  on  both  sides,  but  diminished.  No  Kernig;  no 
Babinski ;  no  Oppenheim;  no  paralyses. 

Skin :  Few  ecchymotic  spots  over  arms  and  legs 
(traumatic?).     No  tache. 

May  13:  Lumbar  puncture:  30  cubic  centimetres  of  very 
turbid  fluid  under  increased  tension  removed;  25  cubic  centi- 
metres antimeningococcus  serum  injected.  Examination  of 
Fluid:  Cytology,  polynuclears  100  per  cent.;  bacteriology, 
smears  show  intra-  and  extracellular  Grain-negative  reni- 
form  diplococcus;  culture  shows  no  growth;  albumin  2  mm.; 
reduction  0. 

May  20:  On  admission,  patient  showed  signs  of  an  acute 
12 


178       MENINGOCOCCUS  MENINGITIS 

encephalitis  and  no  special  symptoms.  Following  lumbar 
puncture  and  injection  of  serum,  temperature  dropped  from 
104.2°  F.  to  normal,  with  immediate  improvement.  Delirium 
ceased.  Slight  external  rectus  palsy  on  right  side  disappeared. 
No  Kernig  or  rigidity.     Patient  now  well  and  sits  up  in  bed. 

May  27 :  To-day  noted  distinct  paralysis  of  left  lower 
extremity :  is  unable  to  pull  it  up.  Distinct  atrophy  of  muscles 
of  thigh  and  leg ;  absence  of  reflex. 

June  10:  General  condition  good;  patient  out  of  bed. 
Paralysis  of  leg  has  improved,  although  walk  is  unsteady. 
Knee-jerk  present.  Some  slight  weakness  of  left  abdominal 
muscle. 

June  22:  Leg  gradually  improving,  although  it  is  still 
dragged  somewhat.     Discharged  well. 

Sensory. — Cutaneous  and  muscular  hyperesthe- 
sia may  at  times  be  so  pronounced  as  to  constitute 
a  veritable  complication.  It  may  be  localized  or 
general. 

OCULAR  COMPLICATIONS 

In  the  earlier  literature  but  slight  attention  was 
paid  to  the  visual  apparatus  in  this  disease.  This 
is  partly  owing  to  the  fact  that  grave  and  permanent 
lesions  are  but  seldom  present.  The  milder  disturb- 
ances are  often  so  fleeting  in  character  that  unless 
specially  looked  for  they  are  likely  to  escape 
observation. 

The  pathogenesis  of  the  ocular  manifestations  of 
this  disease  varies  with  the  seat  of  the  morbid  process. 


COMPLICATIONS  AND  SEQUELS      179 

We  may  distinguish  two  types  of  symptoms:  First, 
those  referable  to  the  various  membranes  and  media 
of  the  eyeball  and  the  tissues  of  the  orbit,  such  as  the 
conjunctiva,  cornea,  sclera,  iris,  choroid,  and  cellular 
tissue  of  the  orbit.  These  are  due  either  to  direct 
propagation  of  the  inflammatory  process  from  the 
nasopharynx  along  the  lachrymal  duct  or  to  hemato- 
genous infection.  Second,  those  referable  to  the 
neuromuscular  system  of  the  eye:  These  are  due  to 
inflammatory  or  toxic  changes  in  the  brain  or  to 
direct  extension  of  the  inflammatory  process  in  the 
meninges  along  the  arachnoid  sheaths  of  the  nerves 
of  the  eye.  The  former  group  of  symptoms  have 
apparently  no  direct  connection  with  the  morbid 
changes  in  the  meninges.  The  eye  lesions  often 
appear  simultaneously  with  those  of  the  meninges. 
Occasionally  they  precede  them.  The  symptoms  of 
neuromuscular  origin,  dependent  as  they  are  upon 
the  meningeal  changes,  are  usually  more  pronounced 
and  severe  in  the  protracted  cases. 

Conjunctivitis. — Acute  catarrhal  conjunctivitis 
is  quite  frequent  in  the  first  few  days  of  the  disease. 
Shaw  found  it  in  60  per  cent,  of  the  Belfast  cases. 
The  meningococcus  is  generally  absent  from  the  dis- 
charge, but  it  has  been  found  by  Koplik,  Robinson, 
and  others.  Conjunctivitis  is  occasionally  present  at 
a  more  advanced  stage  of  the  disease.     It  is  then 


180       MENINGOCOCCUS  MENINGITIS 

probably  due  to  the  constant  exposure  of  the  eyes 
present  in  coma. 

Conjunctival  Hemorrhages. — Though  rarely  pre- 
sent, they  are  of  great  aid  in  the  differential  diag- 
nosis, as  they  are  practically  never  seen  in  other  forms 
of  meningitis. 

Keratitis. — Infiltration  and  steaminess  of  the 
cornea  are  quite  frequent  in  cases  of  protracted  coma. 
In  severe  cases  superficial  corneal  ulcers  may  develop. 
They  usually  heal  without  perforation. 

Iridochoroiditis  (Metastatic  Ophthalmia) . — As 
we  shall  see  later,  the  early  occurrence  of  this  grave 
but  fortunately  rare  complication  has  an  important 
bearing  upon  the  question  of  the  mode  of  infection 
in  this  disease.  Though  it  has  been  seen  in  mild  as 
well  as  in  severe  cases,  it  occurs  most  frequently  in 
the  malignant  type  and  in  cases  of  meningococcasmia 
in  which  meningitis  does  not  develop.  It  is  usually 
unilateral.  Sympathetic  ophthalmia  of  the  other  eye 
is  never  seen.  This  complication  may  appear  at  any 
stage  of  the  disease,  but  is  most  frequent  in  the  first 
few  days.  Within  the  last  few  years  a  noticeable 
diminution  in  the  frequency  of  this  complication  has 
taken  place.  It  is  probably  attributable  to  the  early 
employment  of  the  specific  serum. 

Within  a  few  days  from  the  onset  moderate 
chemosis  and  exophthalmus  set  in,   and  the  media 


COMPLICATIONS  AND  SEQUELS      181 

become  slightly  turbid.  A  purulent  exudate  collects 
in  the  anterior  chamber;  the  eye  becomes  soft,  and  a 
yellow  reflex  is  seen  from  the  depth  of  the  pupil. 
At  a  later  stage  the  injection  and  swelling  of  the 
conjunctiva  diminish,  the  cornea  becomes  clear;  the 
softness  of  the  eyeball,  however,  becomes  more 
marked.  The  exudate  in  organizing  drags  on  the 
retina  and  causes  its  detachment.  In  the  final  stage 
the  bulb  atrophies,  the  lens  becomes  opaque,  and 
complete  loss  of  vision  ensues.  More  rarely  the 
course  of  the  affection  is  still  more  stormy,  pano- 
phthalmia and  perforation  occurring  within  a  few 
days. 

Orbital  Cellulitis. — This  rare  complication  is 
probably  the  result  of  direct  extension  of  the  naso- 
pharyngeal inflammation  into  the  orbit  along  the 
accessory  sinuses  of  the  skull.  Suppuration  of  the 
orbital  tissue  occasionally  results. 

Disturbances  of  the  Extrinsic  Ocular  Muscles. — 
In  the  chapter  on  Symptomatology  we  have  noted 
the  frequent  occurrence  of  symptoms  referable  to  the 
extrinsic  muscles  of  the  eye.  They  are  not  constant, 
but  change  from  day  to  day,  and  at  times  even  during 
a  single  examination.  This  is  due  to  the  fact  that 
they  are  spasmodic  in  nature  and  the  result  of 
cortical  irritation.  Persistent  paralysis  of  the  ocular 
muscles,  seen  so  commonly  in  tuberculous  meningitis, 


182       MENINGOCOCCUS  MENINGITIS 

is  comparatively  rare  in  this  form  of  meningitis. 
When  present,  it  occurs  in  the  form  of  unilateral 
paralysis  of  the  abducens.  Paralysis  of  the  third 
nerve,  manifested  in  ptosis,  divergent  strabismus,  or 
total  ophthalmoplegia,  is  much  less  common.  Pa- 
ralyses of  the  extrinsic  ocular  muscles,  when  present, 
are  seen  most  frequently  at  the  height  of  the  disease, 
and  almost  always  disappear  completely  during 
convalescence. 

Disturbances  of  the  Intrinsic  Ocular  Muscles. — 
The  various  pupillary  changes  which  so  frequently 
accompany  the  disease  have  been  described  in  the 
chapter  on  Symptomatology.  They  are  usually  so 
mild  in  character  and  of  such  brief  duration  that  they 
can  hardly  be  considered  as  complications. 

Amaurosis. — This  dreaded  complication,  which 
fortunately  is  somewhat  rare,  may  be  seen  in  all 
types  of  meningococcus  meningitis.  It  is,  however, 
by  far  most  frequent  in  the  posterior  basic  cases. 
It  usually  occurs  at  an  advanced  stage  of  the  disease 
and  is  almost  always  bilateral.  The  failing  vision 
may  develop  so  insidiously  that  for  a  considerable 
time  it  may  not  be  perceived  by  the  patient.  In 
other  cases,  which  are  less  frequent,  it  first  appears 
on  the  third  or  fourth  day  of  the  disease,  and  within 
a  few  weeks  incurable  blindness  ensues.  In  other 
cases  the   amaurosis   is   sudden  and  complete,   but, 


COMPLICATIONS  AND  SEQUELS      183 

after  a  period  lasting  from  a  few  days  to  several 
months,  gradual  recovery  takes  place.  In  most  of 
the  chronic  cases  associated  with  hydrocephalus, 
there  is  evidence,  on  ophthalmoscopic  examination,  of 
more  or  less  pronounced  stasis  and  optic  neuritis. 
At  a  later  stage  optic  atrophy  is  almost  always 
present.  In  cases  of  sudden  amaurosis  there  are  at 
times  no  abnormal  changes  in  the  fundus.  It  is 
assumed  that  the  blindness  in  these  cases  is  due  to 
transitory  oedema  of  the  visual  centres  in  the  cortex. 

AURAL    COMPLICATIONS 

Otitis  Media. — Acute  catarrhal  otitis  media  is  an 
early  and  frequent  complication  of  meningococcus 
meningitis.  Goeppert  found  it  in  35  per  cent,  of  his 
cases  during  the  first  week  and  in  75  per  cent,  during 
the  second  and  third  weeks.  It  so  rarely  gives  rise  to 
subjective  symptoms  that  its  presence  is  likely  to  be 
overlooked  unless  the  ears  are  examined  at  frequent 
intervals.  Spontaneous  perforation  of  the  drum 
membrane  is  very  rare.  In  some  cases  suppuration 
of  the  middle  ear  occurs.  Involvement  of  the  mastoid 
cells  is  extremely  rare. 

Deafness. — This  is  one  of  the  most  frequent  of 
the  serious  complications  of  meningococcus  menin- 
gitis.    It  is  most  often  seen  in  the  severe  cases,  but 


184       MENINGOCOCCUS  MENINGITIS 

its  occurrence  has  been  reported  in  mild  and  even 
abortive  cases.  There  are  recorded  in  the  literature 
epidemics  of  meningitis  in  which  a  large  proportion 
of  the  patients  developed  this  complication.  Some 
of  these  epidemics  were  of  an  extremely  mild  type. 
It  is  almost  always  bilateral  and  is  seen  most  fre- 
quently at  an  early  period  of  the  disease.  This  com- 
plication is  especially  to  be  dreaded  in  childhood,  as 
in  children  below  seven  to  eight  years  of  age  it  almost 
always  leads  to  associated  mutism.  How  frequently 
this  disease  plays  a  role  in  the  production  of  deaf- 
mutism  is  shown  in  the  following  statistics,  taken 
from  Gassot's  thesis: 

Castex  attributes  40  cases  among  178  acquired  deaf- 
mutes  to  meningococcus  meningitis. 

St.  Hilaire  attributes  44  cases  among  90  acquired  deaf- 
mutes  to  meningococcus  meningitis. 

Bezold  attributes  6  cases  among  70  acquired  deaf-mutes 
to  meningococcus  meningitis. 

Kichhefel  attributes  4  cases  among  15  acquired  deaf- 
mutes  to  meningococcus  meningitis. 

Denker  attributes  16  cases  among  32  acquired  deaf-mutes 
to  meningococcus  meningitis. 

Haberman  attributes  100  cases  among  1137  acquired  deaf- 
mutes  to  meningococcus  meningitis. 

Love  attributes  13  cases  among  80  acquired  deaf-mutes 
to  meningococcus  meningitis. 


COMPLICATIONS  AND  SEQUELAE      185 

Pathologic  Anatomy  and  Pathogenesis. — During 
the  acute  stage  the  purulent  exudate  extends  along 
the  trunk  of  the  auditory  nerve  into  the  internal 
auditory  canal,  where  the  auditory  and  facial  nerves 
are  found  embedded  in  pus.  The  purulent  infiltra- 
tion spreads  to  the  modiolus,  utricle  and  saccule,  and 
along  the  ramifications  of  the  vestibular  nerve.  At 
a  more  advanced  stage  of  the  inflammatory  process 
the  vestibule  is  filled  with  pus  and  the  delicate  organs 
of  audition  and  equilibrium  suffer  destruction.  The 
exudate  may  break  through  the  fenestra  ovale  into 
the  middle  ear.  In  rare  cases  parts  of  the  cochlea 
and  the  organ  of  Corti  remain  unaffected,  permitting 
the  perception  of  a  certain  number  of  tones. 

As  a  result  of  the  organization  of  the  exudate,  the 
cavities  of  the  internal  ear,  the  fenestra?  ovale  and 
rotunda,  and  the  internal  auditory  canal  become  filled 
up  with  proliferating  cicatricial  and  osteoid  tissue. 
The  trunk  and  terminal  filaments  of  the  auditory 
nerve  degenerate  and  become  atrophied. 

A  number  of  theories  have  been  advanced  in  ex- 
planation of  the  mode  by  which  infection  of  the 
internal  ear  takes  place.  The  early  theory  of 
Boucheron,  that  it  is  due  to  spread  of  the  inflammation 
from  the  middle  ear,  is  untenable.  We  have  seen  how 
mild  the  middle-ear  inflammation  is  and  how  rarely 
it  leads  to  spontaneous  perforation  of  the  tympanic 


186       MENINGOCOCCUS  MENINGITIS 

membrane.  Moos  attributes  the  infection  of  the 
internal  ear  to  thrombosis  of  the  arteries  of  the  audi- 
tory nerve,  which  is  derived  from  the  middle  menin- 
geal artery.  As  the  arterial  supply  of  the  facial 
nerve  comes  from  another  source  (stylomastoid 
artery),  this  would  explain  the  rarity  of  serious 
lesions  of  the  facial  nerve.  The  view  generally  ac- 
cepted now,  however,  is  that  the  inflammatory  process 
spreads  by  contiguity  along  the  arachnoid  sheath  of 
the  auditory  nerve.  The  question  as  to  the  primary 
localization  of  the  infection  in  the  internal  ear  has 
not  yet  been  satisfactorily  answered.  Some  writers 
assume  the  spread  of  the  inflammation  along  the 
aqueduct  of  the  cochlea  and  subsequent  infection  of 
the  perilymph;  others  its  spread  into  the  vestibule 
along  the  terminal  filaments  of  the  auditory  nerve. 
The  relative  escape  of  the  facial  nerve  is  attributed 
to  the  fact  that  the  trunk  of  this  nerve  forms  a  com- 
pact bundle  which  does  not  permit  the  penetration 
of  the  purulent  exudate  among  its  fibres. 

Clinical  Course. — The  deafness  usually  appears 
suddenly  in  the  first  few  days  of  the  disease;  rarely 
later  than  the  first  week.  It  is  almost  always  bilateral, 
complete,  and  permanent.  In  a  very  small  number 
of  cases  which  are  due  to  temporary  oedema  of  the 
labyrinth,  the  deafness  is  only  temporary.  There 
may  not  be  complete  loss  of  sound  perception.    In  a 


COMPLICATIONS  AND  SEQUELvE      187 

few  cases  only  a  certain  number  of  notes  are  in- 
audible. Bone  conduction  suffers  equally  with  air 
conduction.  Children  below  seven  to  eight  years 
become  deaf-mutes.  Even  if  this  complication  sets 
in  after  speech  has  begun,  it  ultimately  leads  to  its 
disappearance.  Speech  is  at  first  monotonous,  then 
incomprehensible,  and  finally  lost.  Between  the  ages 
of  eight  and  fifteen  years,  the  verbal  function  is  pre- 
served but  is  altered  and  diminished.  Preservation 
of  audibility  of  some  notes,  even  if  only  slight,  plays 
an  important  role  in  the  success  of  subsequent 
instruction. 

VISCERAL  COMPLICATIONS 

The  visceral  complications  of  meningococcus 
meningitis  are  comparatively  rare.  The  meningo- 
coccus has  a  selective  action  only  on  the  meninges. 
It  is  probable  that  only  when  present  in  large 
numbers  in  the  blood  do  metastatic  foci  in  the  viscera 
occur.  But,  though  greater  success  has  attended  the 
recent  efforts  at  its  discovery  in  the  blood,  the  number 
of  organisms  present  in  this  tissue  has  been  very 
small.  It  is  therefore  not  surprising  that  visceral 
lesions  due  to  the  immediate  presence  of  the  menin- 
gococcus are  rare.  From  a  perusal  of  the  literature 
we  might  gain  the  erroneous  impression  that  the 
meningococcus  is  quite  frequently  found  in  tissues 


188       MENINGOCOCCUS  MENINGITIS 

other  than  the  meninges  and  mucous  membrane  of  the 
respiratory  tract.  This  is,  however,  due  to  the  rela- 
tive preponderance  of  complications  and  unusual 
features  among  the  cases  considered  worthy  of  being 
permanently  recorded. 

Arthropathy. — Epidemics  show  marked  varia- 
tions as  regards  the  frequency  of  the  incidence  of  this 
complication.  The  recent  epidemic  in  New  York 
was  notable  for  the  small  number  of  cases  in  which 
there  was  involvement  of  the  joints.  The  affection 
of  the  joints  may  show  all  grades  of  severity.  Usually 
the  symptoms  are  very  mild  and  transitory.  Occa- 
sionally mild  pain  is  the  only  manifestation  of  the 
arthropathy.  In  other  cases  there  are,  in  addition 
to  the  pain,  local  tenderness,  swelling,  redness,  and 
moderate  effusion  into  the  joint.  These  symptoms 
usually  disappear  in  a  few  days.  In  other  much  less 
frequent  cases  there  are  marked  redness,  local  heat, 
periarticular  oedema,  and  severe  pain.  In  these 
suppuration  occasionally  takes  place.  Even  when 
this  occurs,  healing  usually  takes  place  readily  with- 
out the  production  of  permanent  rigidity  or  ankylosis. 
A  number  of  joints  may  become  involved  simultan- 
eously or  in  succession.  Unlike  gonorrhoeal  arthritis, 
the  periarticular  structures,  such  as  the  bursas  and 
tendons,  are  rarely  involved. 

Respiratory. — These     complications     were     fre- 


COMPLICATIONS  AND  SEQUELAE      189 

quently  seen  in  the  earlier  epidemics  of  Europe  and 
the  United  States.  In  the  more  recent  epidemics 
they  have  been  less  often  observed.  Bronchitis  may 
be  seen  early  in  the  disease.  At  times  it  has  preceded 
the  onset  of  the  meningeal  symptoms.  Pneumonic 
attacks,  both  lobar  and  lobular,  are  seen  occasionally. 
In  some  cases  they  are  undoubtedly  due  to  aspiration 
of  the  vomitus  during  coma.  Jacobitz  has  described 
an  epidemic  in  which  pneumonia  due  to  the  meningo- 
coccus was  present  in  all  the  cases.  In  some  menin- 
gococcus pneumonia  was  present  without  any  evi- 
dence of  meningitis.  The  pneumonic  lesions  at  times 
show  the  simultaneous  presence  of  both  the  pneumo- 
coccus  and  meningococcus. 

Positive  Blood  Culture.  Lobar  Pneumonia  as  Com- 
plication.— M.  K.,  age  14  years  ;  admitted  August  19,  1906 ; 
died  September  23,  1906. 

Family  and  Past  History. — Negative. 

Present  History. — Has  not  felt  quite  well  for  past  three 
weeks.  Had  some  cough  (no  expectoration)  and  occasional 
headache.  One  week  ago  vomited  and  complained  of  head- 
ache and  vertigo,  but  was  better  next  day.  On  day  of  ad- 
mission, feels  feverish  and  chilly  and  has  vomited  and  com- 
plains of  some  headache.     Has  rash  on  body. 

Examination  (August  20). — On  admission  (August  19) 
mind  was  clear  and  patient  responded  quickly  to  questions. 
To-day  patient  is   apathetic,   can   be   roused  only   with  the 


190       MENINGOCOCCUS  MENINGITIS 

greatest  difficulty.  Cries  out  frequently  during  examination ; 
complains  of  severe  pain  in  head. 

Neck  shows  slight  rigidity. 

Eyes:  No  palsies.  Pupils  negative.  Conjunctivae 
slightly  congested;  small  hemorrhage  in  left  ocular  con- 
junctiva. 

Skin:  Profuse  petechial  rash  over  abdomen,  chest,  and 
arms.  Lesions  vary  from  pin-point  to  pin-head  in  size;  some 
are  fading. 

Lungs :  Negative.  Respirations  irregular  in  depth  and 
frequency. 

Heart :  Action  irregular  in  force  and  frequency.  Blow- 
ing systolic  murmur  at  apex,  not  transmitted.  First  sound 
reduplicated.  Systolic  murmur  at  pulmonic  region  over 
vessels  of  neck. 

Extremities :     Negative.     No  Kemig  or  Babinski. 

Clinical  Notes. — August  21 :  Case  admitted  as  typhoid 
suspect;  Widal  reaction  negative.  Blood  culture  positive 
for  meningococci  (Dr.  Libman).  Lumbar  puncture:  30  c.c. 
cloudy  fluid  obtained  under  pressure;  meningococci  present. 
During  preceding  twenty-four  hours  patient  rapidly  becom- 
ing worse.  Can  no  longer  be  roused.  Stuporous  most  of  the 
time.  Frequently  cries  out  at  top  of  voice ;  sometimes  sings. 
Rigidity  of  neck  marked.  Twitchings  of  muscles  of  face, 
more  marked  on  left  side.  Twitching  of  fingers.  Tache 
cerebrale  pronounced.  Kernig  is  now  marked.  (Symptoms 
much  relieved  after  lumbar  puncture.)  Eight  blood  counts 
on  successive  days  (August  19  to  29)  show  leucocytosis 
varying  between  16,000  and  40,000  with  polynuclears  from 
76  per  cent,  to  90  per  cent.     Red  cells  normal. 


COMPLICATIONS  AND  SEQUELAE      191 

August  22:  Blood  culture  positive  for  meningococci 
(Dr.  Libman). 

August  31 :  Condition  not  materially  changed  since 
lumbar  puncture.  Temperature  irregular  and  high  (102°  to 
104.5°  F.).  Pulse  slow  and  of  good  quality.  Patient  eats 
well ;  appetite  good.  Sleeps  well,  as  a  rule ;  requires  hypnotic 
only  occasionally. 

September  3  to  September  18:  Six  blood  counts  on  differ- 
ent days  show  leucocytosis  varying  between  17,000  and 
25,000  with  80  per  cent,  to  90  per  cent,  polynuclears. 

September  6:  During  past  week  general  condition  has 
slowly  become  worse.  Temperature  remains  between  102° 
and  104°  F.  Pulse  more  rapid  and  of  poor  quality.  Patient 
takes  nourishment  poorly  and  is  slowty  emaciating.  Menin- 
geal signs  unchanged.  Mental  condition  slowly  becoming 
clouded.     Severe  general  bronchitis. 

September  10:  Temperature,  which  for  a  few  days  had 
been  running  a  lower  course,  suddenly  rose  and  continued 
high  (104°  F.).  General  condition  much  poorer.  Pulse 
more  rapid  and  feeble,  up  to  140.  Meningeal  signs  un- 
changed. Extremely  apathetic;  takes  very  little  nourish- 
ment.    Has  developed  consolidation  of  whole  of  left  lung. 

September  12:  Lumbar  puncture:  14  cubic  centimetres 
of  brownish  fluid  obtained  under  low  pressure.  Mental  condi- 
tion somewhat  improved. 

September  15:  General  condition  the  same.  Emaciation 
continues.  Signs  of  consolidation  still  present.  Temperature 
lower,  between  101°  and  103°  F.  Pulse  somewhat  slower  and 
of  slightly  better  quality.  Respirations  somewhat  slower  and 
less  labored.     Xo  cyanosis. 


192       MENINGOCOCCUS  MENINGITIS 

September  19:  Lumbar  puncture:  35  cubic  centimetres 
of  cloudy  straw-colored  fluid  obtained  under  some  pressure. 
Report:     Meningococci  present,  no  pneumococci. 

September  22 :  Leucocytes  28,000 ;  polynuclears  92  per 
cent. 

September  23 :  General  condition  gradually  became 
poorer.  Temperature  came  down.  Signs  of  consolidation 
still  present,  but  resolving.  Signs  of  meningitis  remained 
marked  to  the  end.     Died. 

Pleurisy,  with  effusion  of  serum,  pus,  or  blood, 
when  present,  is  always  associated  with  pneumonia. 
It  is  often  not  recognized  during  life. 

Cardiac. — Complications  referable  to  the  heart 
are  relatively  rare  in  this  disease.  In  a  small  number 
of  cases  meningococci  have  been  found  in  the  vegeta- 
tions. Most  of  the  other  complications,  such  as  peri- 
carditis and  myocarditis,  are  usually  first  discovered 
at  autopsy. 

Digestive. — Vomiting  is  occasionally  a  very  per- 
sistent symptom.  When  frequent  it  is  usually  of 
grave  omen.  Diarrhoea  is  seen  quite  frequently  in 
infants  and  young  children.  This  is  not  surprising 
when  the  multiplicity  of  the  lesions  in  the  gastro- 
intestinal tract  is  considered. 

Liver. — Slight  icterus  is  occasionally  seen.  Its 
appearance  on  the  first  day  is  considered  by  Goep- 
pert  to  be  a  sign  of  sepsis. 


COMPLICATIONS  AND  SEQUELAE      193 

Geni to-urinary  Tract. — The  rare  occurrence  of 
hemorrhagic  nephritis  has  been  reported  in  the  litera- 
ture. Multiple  abscesses  of  the  kidney  are  occasion- 
ally seen.  Meningococci  have  been  demonstrated  in 
these  foci  by  Ghon  and  Weichselbaum.  Meningo- 
coccus pyelitis  has  never  been  encountered  by  us. 
Suppurative  cystitis  is  occasionally  observed  in  in- 
fants. In  a  case  of  suppurative  epididymitis  and 
vesiculitis,  Pick  has  been  able  to  find  the  meningo- 
coccus. Incontinence  of  urine,  not  infrequently  asso- 
ciated with  retention,  is  often  present.  We  must 
guard  against  overlooking  this  important  complica- 
tion. 

Skin. — Furunculosis  has  at  times  been  seen.  In 
chronic  cases  bed-sores  over  the  sacrum,  occiput,  and 
heels  are  not  infrequent. 

SEQUELAE  OF  MENINGOCOCCUS  MENINGITIS 

Psychic  disturbances,  as  might  well  be  expected, 
represent  the  most  frequent  sequela?  of  this  disease. 
We  have  seen  that  the  paralyses  occurring  in  this 
disease  are  usually  of  a  transitory  character.  The 
sensory  disturbances,  such  as  deafness  and  blindness, 
though  usually  permanent,  can  not  be  considered  as 
sequelae,  since  most  often  they  make  their  appearance 
before  convalescence  has  begun.  The  psychic  dis- 
turbances,  however,   usually   first   become    manifest 

13 


194       MENINGOCOCCUS  MENINGITIS 

after  the  acute  disease  has  run  its  course.  They  are 
more  frequent  in  the  young.  Hereditary  neuro- 
pathic tendencies  seem  to  play  an  important  role  in 
their  causation.  Most  frequently  they  are  due  to 
irritation  of  the  cortical  cells,  more  rarely  to  hemor- 
rhages or  foci  of  softening  in  the  brain.  The  fre- 
quency of  these  complications  is  shown  in  the  fol- 
lowing : 

Voisin  and  Paisseau  in  60  per  cent,  of  their  cases. 
Netter  in  20  per  cent,  of  his  cases. 
Therod  in  50  per  cent,  of  his  cases. 
Clos  in  40  per  cent,  of  his  cases. 

Infants  and  young  children  frequently  exhibit 
marked  change  in  character.  They  become  violent, 
tyrannical,  brutal,  and  very  irritable.  At  times  they 
exhibit  sudden  paroxysms  of  anger.  They  become 
emotional,  timid,  or  cowardly.  They  often  cry  or 
laugh  without  any  cause ;  nightmare  may  be  frequent. 
Some  suffer  from  headaches,  others  from  dizziness, 
and  even  petit  mat.  In  more  severe  cases  the  appear- 
ance of  speech  is  delayed,  the  face  is  stupid,  the 
memory  feeble,  and  there  is  lack  of  concentration. 
In  adults  there  may  be  apathy,  intellectual  torpor, 
and  mental  confusion.  Some  are  retiring,  while 
others  show  immense  egotism.  Loss  of  memory  is 
very  frequently  observed.     Others  suffer  from  lack 


COMPLICATIONS  AND  SEQUELS      195 

of  concentration.  In  some  the  function  of  ideation 
is  affected.  Double  personality  is  occasionally  ex- 
hibited. The  following  table,  from  Goeppert,  shows 
the  frequency  and  duration  of  the  psychic  sequelae  in 
this  disease.  The  data  of  Goeppert  were  obtained  at 
the  time  the  patients  were  discharged  from  the  hospi- 
tal, those  of  Altmann  and  Cohn  after  six  months 
and  two  years. 


Goeppert. 

Altmann. 

Cohn. 

Survived 

Entirely  well 

Psychic  disturbances 

Weakness  of  memory 

Imbecility 

Sudden  paroxysms  of  anger. 
Headache 

175=26.5% 
125  =  77% 
5=  4.5% 

4=  2.75% 

42 

23=55% 
6  =  14% 
3=  7% 
3=  7% 
3=  7% 

23 

3  =  13% 
3  =  13% 

over  4 

The  prognosis  of  these  disturbances  is  uncertain. 
In  adults  it  is  more  frequently  persistent.  It  has  been 
estimated  by  Looft  that  3.7  per  cent,  of  539  idiots 
were  the  result  of  meningococcus  meningitis.  Netter 
attributes  a  considerable  number  of  these  cases  to 
insufficient  serotherapy. 


Bibliography 

Niemeyer:    Die  epidemischc  cerebrospinal  Meningitis,  Berlin, 

1865. 
Hirsch:     Die  Meningitis  Cerebrospinalis  Epidemica,  Berlin, 

1866. 


196       MENINGOCOCCUS  MENINGITIS 

Moos:        Ueber      Meningitis      Cerebrospinalis      Epidemica, 

Heidelberg,  1881. 
Steinbriigge:     Arch.  Otol.,  1886,  xvi,  14. 
Habermann:     Prag  Zeit.   f.   Heilkd.,  1886,  xi,  27. 
Lejden:    Zeit.  f.  klin.  Med.,  1887,  xii,  385. 
Councilman,  Mallory  and  Wright:     Report  State  Board  of 

Health  of  Mass.,  Boston,  1898. 
Netter:     Twentieth  Century  Practice,  New  York,  1899,  xvi, 

143. 
Gradenigo:    Ann.  des  Malad.  de  POreille,  1899,  xv,  153. 
Gassot:      Contrib.    a    Petude    de   la    Surdi-mutite :  These  de 

Paris,  1903-04. 
Koplik:    Med.  News,  1904,  lxxxiv,  1065. 
Heine:     Berl.  klin.  Wochenschr.,  1905,  xliii,  772. 
Wiechselbaum  and  Ghon:    Wien.   klin.  Wochenschr.,   1905, 

xviii,  625. 
Altmann:    Klin.  Jahrbuch,  1906,  xv,  Heft  3,  627. 
Goeppert:     Klin.  Jahrbuch,  1906,  xv,  313. 
Robinson:    Penna.  Hosp.  Bull.,  1906,  N.  S.  cxxxi,  603. 
Jacobitz:    Zeit.  f.  Hyg.  u.  Infect,,  1907,  lvi,  175. 
Pick:    Berl.  klin.  Wochenschr.,  1907,  xliv,  947. 
Cohn:    Berl.  klin.  Wochenschr.,  1909,  xlvi,  53. 
Paisseau  and  Voisin:    Bull,  et  Mem.  Soc.  Med.  d'Hop.,  1910, 

xxix,  670. 


CHAPTER  XI 

Internal  Hydrocephalus 

By  the  term  internal  hydrocephalus  we  under- 
stand the  abnormal  accumulation  of  cerebrospinal 
fluid  or  exudate  in  the  dilated  ventricles  of  the  brain. 
This  serious  and  important  complication  occurs  fre- 
quently at  one  stage  or  another  of  meningococcus 
meningitis.  Indeed  it  is  present  to  a  more  or  less 
marked  degree  in  all  cases  running  a  subacute  or 
chronic  course.  The  symptoms  ascribable  to  this 
change  in  the  condition  of  the  brain  were  first  de- 
scribed by  Foerster  in  1883  and  further  elaborated 
by  v.  Ziemssen  and  Hesse  in  a  classical  paper  on  the 
subject. 

Pathologic  Anatomy  and  Pathogenesis. — Dilata- 
tion of  the  cisterna  magna  is  usually  seen  in  chronic 
hydrocephalus.  The  arachnoid  membrane  forming 
the  posterior  wall  of  this  cisterna  may  be  markedly 
thickened.  In  some  cases  the  foramen  of  Magendie 
is  obliterated  as  a  result  of  adhesion  between  the  cere- 
bellum and  medulla.  Where  this  has  taken  place,  the 
cisterna  magna  is  only  slightly  developed.  The  fora- 
mina of  Luschka  (the  lateral  outlets  of  the  fourth 
ventricle)  are  usually  dilated.    Closure  of  these  fora- 

197 


198       MENINGOCOCCUS  MENINGITIS 

mina  rarely  takes  place,  on  account  of  their  being 
protected  by  the  cerebellar  peduncles.  It  can  only 
occur  when  the  arachnoid  becomes  greatly  thickened. 
According  to  Goeppert,  cases  of  hydrocephalus 
can  be  grouped  anatomically  under  three  headings: 

1.  Cases  in  which  there  is  complete  obliteration  of 
the  three  outlets  of  the  fourth  ventricle. 

2.  Cases  in  which  the  foramen  of  Magendie  is 
obliterated  while  the  foramina  of  Luschka  show  com- 
pensatory dilatation. 

3.  Cases  in  which  there  is  no  organic  impediment 
to  the  flow  of  cerebrospinal  fluid  from  the  fourth 
ventricle  into  the  subarachnoid  space.  To  this  ana- 
tomical type  belong  most  of  the  cases  of  hydro- 
cephalus. 

In  these  cases  and  in  those  belonging  to  the 
second  group,  in  which  there  is  compensatory  dilata- 
tion of  the  lateral  foramina  of  Luschka,  three  possible 
factors  may  enter  in  the  production  of  the  distention 
of  the  ventricles, — namely: 

1.  Increase  in  pressure  throughout  the  whole 
ventricular  subarachnoid  space. 

2.  Local  increase  in  intraventricular  pressure  as 
a  result  of  valvular  compression,  which  prevents  the 
flow  of  cerebrospinal  fluid  from  the  ventricles  into  the 
subarachnoid  space. 


INTERNAL  HYDROCEPHALUS         199 

3.  Lack  of  mechanical  resistance  on  the  part  of 
the  ventricular  walls,  which  permits  their  distention 
even  under  moderate  intraventricular  pressure. 

The  first  factor  probably  plays  an  important  role 
in  the  production  of  acute  hydrocephalus  occasionally 
seen  at  the  onset  of  the  disease.  The  intense  in- 
flammatory process  leads  to  a  rapid  production  of 
cerebrospinal  fluid  which  the  channels  of  excretion 
are  unable  to  cope  with.  The  ventricles,  being  sur- 
rounded by  soft  brain  tissue,  yield  readily  to  the  in- 
creased pressure,  and  acute  distention  results.  The 
studies  of  Holm,  Levy,  and  Flexner  on  the  ready 
absorbability  of  the  antimeningococcic  serum  show 
that  there  is  probably  no  marked  interference  with 
the  absorptive  functions  of  the  subarachnoid  space. 

Aside  from  the  cases  in  which  there  is  anatomical 
obliteration  of  the  foramina,  there  are  others  in  which 
there  is  present  a  functional  impediment  to  the  flow 
of  cerebrospinal  fluid  from  the  brain  into  the  cord. 
Though  there  is  a  marked  difference  in  the  pressure 
of  the  fluid  in  the  ventricles  and  spinal  subarachnoid 
space  during  life  and  an  increase  in  the  pressure  in 
the  spine  on  sitting  up  the  patient,  at  post-mortem 
examination  there  is  found  a  ready  communication 
between  the  spaces  in  the  brain  and  cord.  It  is  prob- 
able that  the  outlets  of  the  fourth  ventricle  are 
temporarily  obliterated  by  the  weight  of  the  dilated 


200       MENINGOCOCCUS  MENINGITIS 

lower  horns  pressing  the  cerebellum  down  against 
the  medulla. 

Occasionally  cases  of  hydrocephalus  are  seen  in 
which  there  is  at  no  time  a  marked  increase  in  intra- 
ventricular pressure.  In  a  number  of  such  cases, 
we  have  been  able  to  prove  ready  communicability 
between  the  ventricular  system  and  the  spinal  sub- 
arachnoid space  by  the  injection  of  methylene  blue 
in  the  lateral  ventricles.  Within  fifteen  to  twenty 
minutes,  the  cerebrospinal  fluid  obtained  by  lumbar 
puncture  was  colored  by  the  dye.  It  must  be  as- 
sumed that  the  walls  of  the  ventricles  in  these  cases 
have  lost  their  tone  and  have  been  unable  to  resist 
even  a  moderate  increase  in  pressure  without  be- 
coming stretched.  It  is  not  unlikely  that  the  presence 
of  cachexia  tends  to  produce  this  change  in  the  con- 
dition of  the  walls  of  the  ventricles. 

Clinical  Course. — In  a  most  admirable  paper  on 
the  subject,  Koplik  describes  three  conditions  under 
which  hydrocephalus  may  occur  as  a  complication  of 
meningococcus  meningitis. 

1.  Acute  hydrocephalus  at  the  onset  of  the 
disease. 

2.  Hydrocephalus  complicating  meningococcus 
meningitis  at  any  period  after  the  first  week. 

3.  Hydrocephalus  in  posterior  basic  meningitis. 
The  importance  of  the  early  recognition  of  the 


INTERNAL  HYDROCEPHALUS         201 

appearance  of  hydrocephalus  at  the  onset  of  the  dis- 
ease can  not  be  too  forcibly  emphasized.  The  life  of 
the  patient  may  depend  upon  the  rapidity  with  which 
a  correct  interpretation  of  the  symptoms  is  made  and 
relief  of  the  dangerous  condition  by  lumbar  puncture 
is  instituted.  The  condition  appears  suddenly  and 
usually  within  twenty-four  hours  from  the  onset  of 
the  disease,  with  fever,  vomiting,  and  headache.  The 
patient  suddenly  becomes  pale  or  ashen,  the  surface 
of  the  body  cool,  the  extremities  cyanotic  the  pupils 
dilated,  the  pulse  rapid  and  feeble,  the  respirations 
labored  and  sighing,  and  unconsciousness  rapidly 
sets  in.  In  other  cases  the  onset  of  the  hydrocephalus 
seems  to  coincide  with  the  onset  of  the  disease. 
Stupor  develops  early  and  is  rapidly  followed  by 
coma  and  prostration.  In  very  severe  cases  the 
patients  are  limp,  and  the  symptoms  characteristic  of 
meningitis — such  as  hyperesthesia  or  rigidity  of  the 
neck,  Kernig  sign,  and  opisthotonus — are  absent. 
This  renders  the  diagnosis  all  the  more  difficult,  and 
to  establish  it  we  must  look  very  carefully  for  a  tense 
and  bulging  fontanelle  in  young  infants  or  the  Mac- 
ewen  sign  in  older  children. 

Acute  Hydkck  iimiaus. — P.  S.,  age  7  years;  admitted 
April  18,  1906;  died  April  20,  1906. 

Family  and  Past  History:    Negative. 


202       MENINGOCOCCUS  MENINGITIS 

Present  History. — Sudden  onset  thirty-six  hours  ago  with 
severe  headache  and  fever.  Twenty-four  hours  ago  was  un- 
consciousness, eyes  were  crossed  (had  not  been  before).  Chill 
about  twenty  hours  ago,  followed  by  a  convulsion  lasting 
about  fifteen  minutes.  Has  vomited  several  times  since,  not 
projectile.  There  were  restlessness  and  twitching  of  the 
muscles.  Swallowing  became  very  difficult.  Fever  continued 
very  high.    Has  involuntary  urination  and  defecation. 

Examination. — General  condition  poor.  Child  comatose. 
Pupils  negative.  Presence  of  palsies  could  not  be  determined. 
Head  retracted ;  neck  rigid.  No  tache.  Heart  action  some- 
what irregular  but  of  good  force.  Very  slight  Kernig.  No 
Babinski. 

Clinical  Notes. — April  18:  Two  lumbar  punctures. 
Turbid  fluid  obtained  both  times  under  very  great  pressure. 
Meningococci  found  in  spreads  and  cultures.  Leucocytes 
26,000. 

April  19 :    Regurgitates  feedings  through  nose. 

April  20:  Child  isolated  because  of  presence  of  Klebs- 
Loeffier  bacilli  in  nose  discharge.  Activity  stimulated  and 
intravenous  and  subcutaneous  saline  infusions  given. 
Temperature  kept   on  rising  (to  104.2°  F.).     Child  died. 

The  second  form  of  hydrocephalus  may  occur 
at  any  period  of  the  disease  after  the  first  week. 
Often  it  appears  after  most  of  the  acute  symptoms 
have  subsided  or  become  much  ameliorated.  It  may 
have  a  sudden  or  insidious  onset.  In  the  former  type 
the  temperature  rises,  vomiting  occurs,  the  headache 


INTERNAL  HYDROCEPHALUS         203 

becomes  once  more  very  intense,  the  pupils  dilated, 
the  hyperesthesia  and  rigidity  become  aggravated, 
the  mind  becomes  clouded,  and  sopor  develops.  In 
the  cases  with  insidious  course  the  principal  symp- 
toms are  emaciation,  clouding  of  the  intellect, 
paroxysms  of  vomiting,  headache,  rise  of  tempera- 
ture, paresis  of  the  facial  muscles,  strabismus,  and 
volitional  tremors. 

Progressive  emaciation  is  a  striking  symptom 
which  ultimately  becomes  extreme  despite  the  inges- 
tion of  large  quantities  of  food.  It  differs  from  that 
seen  in  the  course  of  any  other  acute  disease  and 
seems  to  be  trophic  in  nature.  The  skin  becomes  dry 
and  scaly.  A  change  in  the  mental  condition  is  one 
of  the  earliest  indications  of  the  development  of  a 
hydrocephalus.  The  children  show  progressive  loss 
of  interest  in  their  surroundings.  They  lie  perfectly 
quiet  for  hours  at  a  time,  with  eyes  wide  open  and  a 
peculiar  vacant  stare.  Questions  are  answered  in  the 
fewest  possible  words.  They  may  bite  their  nails  or 
scratch  their  nose  and  skin  almost  continuously. 
Food  is  devoured  greedily.  Although  the  mind 
is  apparently  clear,  the  intelligence  even  of  older 
patients  is  no  greater  than  that  of  a  baby  six 
months  of  age.  Other  patients  are  very  excitable 
and  cry  continuously.     Some  suffer  from  paroxysms 


204       MENINGOCOCCUS  MENINGITIS 

of  great  anxiety;  others  have  delirium  or  hallucina- 
tions. In  a  small  number  of  cases  there  is  per- 
sistent unconsciousness,  interrupted  by  convulsions 
which  appear  early  in  the  course  of  the  hydro- 
cephalus. 

From  time  to  time  attacks  of  vomiting  occur. 
These  are  independent  of  the  ingestion  of  food.  At 
a  more  advanced  stage  pareses  of  the  muscles  of  the 
face,  eyes,  and  extremities  make  their  appearance. 
There  are  seen  intention  tremors  of  the  face,  jaws, 
and  extremities.  The  pupils  are  widely  dilated.  The 
eyes  are  turned  downward,  exposing  the  upper 
sclera.  The  pulse  is  irregular  in  rhythm  and  force. 
The  temperature  may  be  normal,  subnormal,  or  inter- 
mittently elevated.  The  reflexes  may  be  absent  or 
exaggerated.  Ankle-clonus,  on  one  or  both  sides, 
is  present  in  some  of  the  cases.  The  Babinski  reflex 
may  be  present  from  time  to  time.  In  practically  all 
the  children  in  which  the  fontanelles  are  closed,  one 
of  the  earliest  indications  of  the  presence  of  hydro- 
cephalus is  a  positive  Macewen  sign. 

Hydrocephalus  is  a  regular  feature  of  the  cases 
belonging  to  the  posterior  basic  type.  Why  this 
should  be  the  case  becomes  apparent  when  we  con- 
sider the  tender  age  of  most  of  the  patients  and  the 
fact  that  the  lesions  are  chiefly  localized  at  the 
posterior  part  of  the  base  of  the  brain.     In  infancy 


INTERNAL  HYDROCEPHALUS         205 

the  soft  brain  tissue  and  the  skullcap  with  its  open 
fontanelle  and  loosely  united  sutures  offer  no  great 
resistance  to  the  accumulation  of  fluid  in  the  ventri- 
cles. To  this  there  is  added  a  mechanical  factor  in 
the  form  of  obliteration  of  the  outlets  of  the  fourth 
ventricle  by  the  inflammatory  exudate  at  the  base  of 
the  brain. 

It  is  very  difficult  to  separate  the  symptoms  refer- 
able to  the  hydrocephalus  from  those  which  are  due 
to  the  meningitis  proper.  Percussion  of  the  skull 
does  not  yield  the  Macewen  sign  in  infants  whose 
fontanelles  are  still  open.  Instead  we  get  the  im- 
pression of  a  sac  with  fluctuating  contents. 

Lumbar  puncture  yields  varying  results.  In 
those  cases  in  which  the  hydrocephalus  develops  at 
the  initial  stage  of  the  disease,  a  considerable  quantity 
of  fluid  under  high  pressure  is  usually  obtainable. 
Where  there  is  mechanical  obstruction  at  the  base 
only  10  or  15  cubic  centimetres  of  fluid  under  little 
or  no  pressure  may  be  obtained.  In  these  cases  the 
pressure  does  not  become  higher  when  the  patient  is 
placed  in  the  sitting  posture  or  is  made  to  cry  or 
breathe  deeply.  In  some  cases  belonging  to  this  type 
only  a  few  drops  of  fluid  can  be  withdrawn.  We  have 
previously  spoken  of  the  difficulties  encountered  in 
the  demonstration  of  the  meningococcus  in  the 
cerebrospinal  fluid  of  patients  who  have  reached  the 


206       MENINGOCOCCUS  MENINGITIS 

chronic  subacute  stage  of  the  disease.  To  establish 
the  diagnosis  in  these  cases  the  history  and  clinical 
features  must  be  studied  with  unusual  care. 

Bibliography 

Foerster:    Path.  Anat.,  1863,  597  (quoted  by  Joslin). 

v.  Ziemmssen  and  Hesse:    Deut.  Archiv  f.  klin.  Woch.,  1865, 

i,  72  and  346. 
v.  Ziemmssen:    Hanclb.  d.  specielle  Path.  u.  Therap.,  Leipzig, 

1874. 
Joslin:    Amer.  Jour.  Med.  Sciences,  1900,  cxx,  444. 
Goeppert:    Klin.  Jahrbuch,  1906,  xv,  313. 
Koplik:   Amer.  Jour.  Med.  Sciences,  1907,  cxxxiii,  547. 
Knox  and  Sladen:    Arch.  Ped.,  1908,  xxv,  761. 
Huber:   Arch.  Ped.,  1908,  xxv,  161. 


CHAPTER  XII 

Diagnosis 

Since  the  introduction  of  specific  serotherapy  the 
importance  of  arriving  at  a  correct  diagnosis  at  the 
earliest  possible  moment  has  become  greatly  en- 
hanced. On  its  early  establishment  is  dependent  in 
large  part  the  success  of  this  mode  of  treatment.  The 
diagnosis  of  the  disease  is  readily  made  in  some  cases. 
It  encounters  insuperable  difficulties  in  other  cases. 
It  must  be  based  upon  the  history  and  clinical  features 
of  the  disease  and  upon  the  results  of  the  laboratory 
examination  of  the  cerebrospinal  fluid,  blood,  and 
the  nasopharyngeal  secretion.  Though  the  examina- 
tion of  the  cerebrospinal  fluid  often  yields  results 
which  clinch  the  diagnosis,  the  importance  of  a  care- 
ful clinical  study  of  each  case  must  not  on  that  ac- 
count be  minimized.  In  the  first  place,  in  order  to 
obtain  cerebrospinal  fluid  for  examination,  definite 
indications  for  the  performance  of  lumbar  puncture 
must  be  present.  These  necessarily  are  derived  from 
a  careful  study  of  the  clinical  features  present  in  the 
individual  case.  Moreover,  we  have  seen  that  occa- 
sionally the  results  of  the  macroscopic,  chemical, 
cytological,  and  bacteriological  study  of  the  cerebro- 

207 


208       MENINGOCOCCUS  MENINGITIS 

spinal  fluid  yield  uncertain  data,  and  we  are  thrown 
back  upon  the  interpretation  of  the  clinical  features 
for  the  establishment  of  the  diagnosis. 

In  this  disease  we  usually  arrive  at  a  final  diag- 
nosis by  two  stages:  First,  we  determine  the  prob- 
able existence  of  a  meningitis;  second,  we  determine 
that  the  meningitis  is  due  to  the  meningococcus.  As 
soon  as  a  tentative  diagnosis  of  meningitis  has  been 
made,  it  becomes  our  duty  to  perform  a  lumbar 
puncture  and  withdraw  fluid  for  examination.  The 
statistics  to  be  cited  later,  showing  to  what  an  extent 
the  success  of  serotherapy  is  dependent  upon  the 
early  administration  of  the  serum,  demand  that  we 
arrive  at  a  diagnosis  without  undue  delay. 

The  clinical  features  of  the  disease  usually  enable 
us  to  make  the  diagnosis  of  meningitis.  Occasionally 
the  clinical  picture  permits  us  to  make  not  only  a 
definite  diagnosis  of  meningitis  but  also  a  probable 
one  of  meningococcus  meningitis. 

Symptoms  that  speak  for  the  presence  of  menin- 
gitis pure  and  simple  are:  Fever,  rapid  pulse  and 
respirations,  headache,  vomiting,  convulsions,  de- 
lirium or  unconsciousness,  restlessness,  pupillary 
changes,  mydriasis  on  flexion  of  the  head  or  irrita- 
tion of  the  skin,  strabismus,  facial  paresis,  hyper- 
esthesia, rigidity  of  the  neck  and  spine,  retraction  of 
the  head,  orthotonus  or  opisthotonus,  tache  cerebrale. 


DIAGNOSIS  209 

bulging  fontanelle  or  Macewen  sign,  Kernig  sign, 
Brudzinski  neck  and  leg  signs. 

The  most  important  of  these  are  hyperesthesia, 
bulging  fontanelle  in  infancy  or  Macewen  sign  in 
older  children  and  adults,  mydriasis  on  attempted 
flexion  of  the  head  or  irritation  of  the  skin,  rigidity 
of  the  neck,  retraction  of  the  head,  Kernig  sign,  and 
Brudzinski's  signs. 

The  additional  features  which  render  it  probable 
that  the  meningitis  is  meningococci  in  nature  are  the 
presence  of  an  epidemic  outbreak  in  the  locality  in 
which  the  patient  resides,  the  sudden  onset  together 
with  the  absence  of  evidence  of  primary  disease  else- 
where, the  presence  of  herpes,  petechias,  evanescent 
erythematous  eruptions,  and  arthropathy.  Moreover, 
the  fact  should  constantly  be  borne  in  mind  that  with 
the  exception  of  tuberculous  meningitis,  which  is 
commonly  readily  distinguishable  from  this  form  of 
meningitis,  by  far  the  largest  proportion  of  cases  of 
primary  meningitis  belong  to  the  meningococci 
variety.  So  that  once  the  diagnosis  of  acute  primary 
meningitis  is  made,  it  becomes  ipso  facto  probable 
that  the  disease  is  meningococcus  meningitis. 

Sources  of  Diagnostic  Error. — Failure  to  make  a 
correct  diagnosis  of  the  disease  is  chiefly  attributable 
to  two  facts:  (1 )  Absence  of  one  or  more  of  the  char- 
acteristic symptoms  of  the  disease:    (2)    prominence 

14 


210       MENINGOCOCCUS  MENINGITIS 

of  one  or  more  symptoms  that  are  more  characteristic 
of  some  other  disease.  In  cases  belonging  to  the  first 
class,  we  are  misled  by  the  non-appearance  of  one  or 
more  of  the  following  symptoms:  fever,  psychic  dis- 
turbances, rigidity  of  the  neck  and  Kernig  sign. 

Cases  are  described  in  the  literature  in  which  the 
temperature  was  normal  during  the  first  few  days 
of  the  disease.  Indeed  in  the  older  descriptions  of 
the  disease,  before  clinical  thermometry  came  into 
general  use,  there  is  frequent  mention  of  the  fact  that 
fever  was  quite  often  absent.  In  the  subacute  and 
chronic  cases  prolonged  periods  of  apyrexia  are  quite 
commonly  seen. 

Psychic  disturbances  are  at  times  so  slight  that 
they  are  easily  overlooked.  The  patients  are  ap- 
parently rational  and  answer  questions  quite  intelli- 
gently. This  is  the  more  striking  when  we  consider 
the  gravity  of  the  condition  and  the  marked  lesions 
which  may  be  present  in  the  meninges,  brain,  and 
cord. 

A  more  serious  source  of  error  is  absence  of  the 
characeristic  rigidity  of  the  neck.  We  instinctively 
expect  this  symptom  to  be  marked  in  all  cases,  and 
when  we  fail  to  detect  it  we  are  likely  to  be  thrown 
off  our  guard  and  thus  overlook  a  number  of  other 
symptoms  which  might  lead  us  to  a  correct  diagnosis. 
Rigidity  of  the  neck  is  not  infrequently  absent,  or  at 


DIAGNOSIS  211 

least  undetected  in  the  very  young  and  very  old 
patients.  It  is  rarely  present  in  the  fulminating 
types  of  the  disease  and  in  the  cases  that  develop 
acute  hydrocephalus  at  the  onset. 

The  Kernig  sign  is  less  frequently  missed,  yet 
cases  are  reported  in  which  this  sign  was  present  at  no 
period  of  the  disease.  It  is  usually  in  the  fulminating 
cases  with  intense  prostration  and  general  relaxation 
that  the  Kernig  sign  is  not  demonstrable. 

In  general,  we  may  guard  against  failure  to  make 
a  diagnosis  in  these  cases  by  bearing  in  mind  the 
fact  that  at  times  some  of  the  characteristic  symp- 
toms may  not  be  manifest. 

On  the  other  hand,  the  prominence  of  certain 
symptoms  may  lead  us  to  assume  the  existence  of  a 
wholly  different  disease,  unless  a  careful  and 
thorough  examination  is  made.  The  intermittent 
temperature  has  not  so  rarely  led  to  confusion  of  this 
disease  with  malarial  fever.  The  paroxysms  in  ter- 
tian malaria,  however,  recur  at  more  regular  intervals 
and  they  are  usually  of  shorter  duration.  The  various 
cutaneous  eruptions  may  give  rise  to  diagnostic  error. 
They  may  lead  to  the  assumption  that  simple  purpura, 
erythema  nodosum,  scarlet  fever,  or  measles  is 
present.  The  diagnosis  of  septicaemia  may  be  based 
upon  the  presence  of  a  petechial  eruption,  if  sufficient 
attention   is   not   paid   to   the  characteristic   rigidity. 


212       MENINGOCOCCUS  MENINGITIS 

Gastro-enteritis  may  be  suspected  when  vomiting 
and  diarrhoea  are  pronounced  symptoms.  Pain  in 
the  joints  may  mislead  us  into  the  diagnosis  of  rheu- 
matic fever,  while  pain  on  lateral  movements  of  the 
head  may  be  attributed  to  a  harmless  torticollis.  We 
can  only  avoid  the  diagnostic  errors  in  this  class  of 
cases  by  a  careful  and  thorough  physical  examination 
of  each  individual  case  and  by  carefully  considering 
the  clinical  picture  as  a  whole. 


CHAPTER  XIII 

DlFFEKEXTI.iL  DIAGNOSIS 

There  are  a  number  of  infectious  diseases  which 
at  times  closely  simulate  meningitis.  The  most  im- 
portant of  these  are  pneumonia,  septicopyemia, 
typhoid,  typhus,  influenza,  tetanus,  and  acute  anterior 
poliomyelitis. 

Pneumonia  and  meningococcus  meningitis  have 
not  infrequently  been  taken  one  for  the  other.  The 
sudden  onset,  with  high  temperature,  chill,  vomiting, 
is  seen  in  both  diseases.  Moreover,  in  both  the  early 
appearance  of  herpes  is  a  frequent  symptom.  De- 
lirium, restlessness,  and  labored  breathing  may  be 
present  in  both  diseases.  The  marked  similarity  be- 
tween the  two  affections  demands  careful  and  re- 
peated examination  of  the  lungs.  The  upper  parts 
of  the  axilla  and  the  interscapular  region  often  show 
the  earliest  signs  of  consolidation.  The  fact,  however, 
must  not  be  lost  sight  of,  that  occasionally  pneumonia 
is  an  early  complication  of  this  form  of  meningitis. 
Needless  to  say  that  if  the  slightest  suspicion  of 
the  existence  of  meningitis  is  entertained,  lumbar 
puncture  must  be  performed  without  undue  delay. 

Typhoid  Fever. — The  insidious  onset  of  this  dis- 
ease is  an  important  differential  point  from  menin- 

213 


214       MENINGOCOCCUS  MENINGITIS 

gococcus  meningitis.  Occasionally,  however,  when 
occurring  in  military  epidemics,  typhoid  may  begin 
with  violent  symptoms.  Features  which  may  be 
common  to  both  diseases  are  epistaxis,  headache,  rest- 
lessness, insomnia,  delirium,  torpor,  diarrhoea,  and  a 
roseolar  eruption.  In  meningitis,  however,  the  head- 
ache is  more  intense.  Vomiting  is  rare  in  typhoid, 
while  diarrhoea  and  abdominal  distention  are  very 
unusual  in  meningitis.  In  the  latter  disease  the  fever 
has  an  irregular  curve,  the  pulse  is  not  markedly  slow, 
the  tongue  not  characteristically  coated,  and  the 
spleen  not  enlarged.  The  Widal  and  diazo  reactions 
and  the  number  of  leucocytes  are  valuable  differential 
criteria. 

Typhus  Fever. — The  similarity  in  the  clinical 
picture  betwen  severe  typhus  and  meningococcus 
meningitis  is  so  marked  that  keen  observers,  like 
Murchison,  have  considered  this  form  of  meningitis 
a  variety  of  typhus.  Indeed  it  is  very  probable  that 
in  the  past  the  two  diseases  were  frequently  con- 
founded. Fortunately,  typhus,  except  in  a  greatly 
attenuated  form,  is  now  rarely  seen  in  this  country. 
Sudden  onset  is  common  to  both.  Other  common 
symptoms  are  purpura,  delirium,  muscular  rigidity, 
and  prostration.  The  eruption  in  typhus  is  usually 
more  gradual  in  development,  whereas  the  petechia? 
and    purpuric    rash    in    meningitis,    when    present, 


DIFFERENTIAL  DIAGNOSIS  215 

usually  appear  within  twenty-four  hours  from  the 
onset.  The  temperature  curve  is  more  regular,  and 
the  delirium  is  a  somewhat  later  manifestation  in 
typhus  fever.  The  diazo-reaction  is  commonly 
present  in  typhus. 

Influenza. — The  nervous  type  may  closely  re- 
semble meningitis.  The  sudden  onset,  with  coryza, 
headache,  pain  in  the  back,  general  soreness,  delirium, 
and  vomiting,  is  not  unlike  that  of  meningitis. 

Septicopycemia. — The  intermittent  or  remittent 
temperature,  the  chills,  the  various  cutaneous  erup- 
tions, such  as  erythema,  purpura,  and  petechial  rash, 
and  arthropathy  may  be  common  to  both  diseases. 
The  onset  in  septicopyemia  is,  however,  usually  in- 
sidious, and  valvular  endocarditis  is  much  more  fre- 
quent. Moreover,  in  many  cases  a  primary  focus  of 
infection  is  to  be  detected  upon  a  thorough  and  careful 
examination.  A  blood  culture  not  infrequently  re- 
veals the  presence  of  the  infecting  organism. 

In  addition  to  the  above  general  infectious  dis- 
eases which  at  times  simulate  meningitis,  there  are 
a  number  of  more  or  less  localized  infections  involv- 
ing the  nervous  tissue  which  may  give  rise  to  con- 
fusion. The  most  important  of  these  are  tetanus, 
poliomyelitis,  polioencephalitis,  and  meningism. 

Tetanus. — The  spinal  rigidity,  opisthotonus,  pain 
in  the  limbs,  and  fever  are  common  features.     Con- 


216       MENINGOCOCCUS  MENINGITIS 

sciousness  is  retained  in  tetanus,  while  in  meningitis 
there  are  usually  no  trismus  and  paroxysmal  con- 
tractures and  pains  which  form  the  dominant  symp- 
toms of  tetanus.  Headache  and  herpes  are  absent  in 
tetanus. 

Poliomyelitis. — The  meningeal  form  of  acute 
anterior  poliomyelitis  at  times  offers  the  greatest 
difficulty  to  the  diagnostician.  Headache,  vomiting, 
convulsions,  rigidity  of  the  neck  may  be  present  for 
several  days  before  the  characteristic  paralyses  have 
made  their  appearance.  Diffuse  or  local  pains  may 
be  felt  in  the  muscles  and  hyperesthesia  may  be 
present.  Mental  symptoms,  however,  are  usually 
only  slight  or  entirely  absent.  In  cases  in  which  the 
paralysis  is  only  slightly  marked,  the  diagnosis  may 
remain  unsettled.  Meningococcus  meningitis,  as  we 
have  seen,  occurs  most  frequently  in  the  winter  and 
spring,  whereas  poliomyelitis  is  most  prevalent  in 
summer  and  autumn.  The  paralyses  in  meningitis, 
being  radicular  in  origin,  are  associated  with  pain 
and  diffuse  muscular  atrophy  and  are  rarely  per- 
manent. On  the  other  hand,  the  paralyses  in  polio- 
myelitis are  usually  not  painful  except  in  the  be- 
ginning. They  are,  as  a  rule,  definitely  localized  to  a 
group  of  muscles  which  become  permanently  para- 
lyzed and  atrophied. 

According  to  Peabody  and  Draper,  the  cerebro- 


DIFFERENTIAL  DIAGNOSIS  217 

spinal  fluid  in  poliomyelitis  possesses  the  following 
characteristics.  It  is  perfectly  clear,  at  times  fine 
white  flakes  may  be  seen,  the  pressure  is  moderate, 
there  is  increase  of  fibrin;  from  the  second  to  the 
fourth  week  there  is  usually  an  increase  of  globulin 
contents. 

Polioencephalitis. — While  this  disease  usually 
closely  resembles  tuberculous  meningitis,  there  are 
certain  types  that  have  a  symptomatology  which  is 
almost  identical  with  that  of  meningococcus  menin- 
gitis. Koplik  has  called  attention  to  the  fact  that  in 
this  disease  there  is  a  short  period  following  the  onset 
of  a  high  fe^  er  during  which  the  patient  continues  to 
be  about,  whereas  in  meningitis  the  prostration  at  the 
onset  is  usually  so  marked  that  he  is  compelled  to 
go  to  bed  at  once.  There  is  also  increasing  sopor 
extending  over  several  days.  Upon  lumbar  puncture 
there  is  withdrawn  a  clear  or  slightly  flocculent  fluid 
containing  90  to  100  per  cent,  lymphocytes  and  no 
bacteria. 

Meningism  (Serous  Meningitis) . — Meningism  is 
a  term  first  employed  by  Dupre  for  a  symptom  com- 
plex occurring  in  the  course  of  a  number  of  acute 
infectious  diseases.  It  is  most  frequently  seen  in 
lobar  and  broncho-pneumonia,  typhoid,  scarlet  fever, 
diphtheria,  and  whooping-cough.  It  is  at  times  very 
difficult  to  distinguish  clinically  this  morbid  process 


218       MENINGOCOCCUS  MENINGITIS 

from  true  meningitis.  The  detection  of  the  existence 
of  a  primary  infection  is  a  point  of  great  importance. 
The  rigidity  of  the  neck  is  usually  moderate  and  not 
present  at  all  times.  The  Kernig  sign  is  rarely  as 
marked  as  in  meningitis.  Mental  disturbances  do  not 
form  as  marked  a  feature.  The  Macewen  sign  and 
the  bulging  of  the  fontanelle  are  not  as  pronounced 
as  in  meningitis.  The  meningeal  symptoms  are  of 
short  duration. 

Meningeal  Hemorrhage. — At  times  this  condition 
is  not  easily  distinguished  from  meningococcus 
meningitis.  In  meningeal  hemorrhage  there  is  rarely 
any  fever.  Indeed  the  temperature  is  at  times  sub- 
normal. The  pulse  is  often  slow  and  of  high  tension. 
Hyperesthesia  is  usually  absent.  Herpes,  arthropa- 
thy, and  cutaneous  eruptions  are  not  seen  in  menin- 
geal hemorrhage.  Psychic  disturbances  are  not 
common.  Meningeal  hemorrhage  is  occasionally 
accompanied  by  subconjunctival  ecchymoses  and 
severe  albuminuria. 

In  infancy  we  must  also  consider  in  the  differ- 
ential diagnosis  the  following  common  conditions, — 
namely,  gastro-enteritis,  infantile  eclampsia,  and 
tetany. 

Gastro-enteritis. — Convulsions  and  various  cere- 
bral symptoms,  as  is  well  known,  are  not  uncommon 
in  the   clinical   picture   of  infantile  gastro-enteritis. 


DIFFERENTIAL  DIAGNOSIS  219 

Some  degree  of  rigidity  of  the  neck  has  at  times  been 
observed.  The  condition  of  the  fontanelle,  when  the 
infant  is  perfectly  quiet,  is  one  of  the  most  valuable 
diagnostic  aids.  Soon  after  the  onset  of  a  severe 
attack  of  gastro-intestinal  disturbance  the  fontanelle 
becomes  depressed,  whereas  in  meningitis,  even  in  the 
presence  of  moderate  diarrhoea,  it  usually  becomes 
tense  and  bulging.  In  older  children  the  presence  of 
Macewen  and  Kernig  signs,  as  a  rule,  differentiates 
meningitis  from  gastro-enteritis. 

Infantile  Eclampsia. — At  the  onset  of  an  eclamp- 
tic seizure,  especially  if  it  is  the  first  attack,  the  exist- 
ence of  meningitis  is  often  suspected, — this  the  more 
readily  as  such  an  attack  frequently  follows  or  is 
accompanied  by  a  sudden  and  sharp  rise  in  tempera- 
ture. We  must  carefully  inquire  into  the  possible 
presence  of  an  etiological  factor,  such  as  a  dietetic 
error.  Bulging  of  the  fontanelle  is  usually  present 
in  eclampsia  during  the  convulsive  seizure,  but  dis- 
appears in  the  intervals. 

Tetany. — In  young  infants  the  differential  diag- 
nosis is  occasionally  difficult.  The  Trousseau  and 
Chvostek  signs  and  the  galvanic  hyperexcitability  are 
not  usually  present  in  meningitis.  On  the  other  hand, 
the  bulging  fontanelle  is  not  a  feature  of  tetany.  In 
some  cases  final  decision  is  only  made  by  lumbar 
puncture. 


220       MENINGOCOCCUS  MENINGITIS 

DIFFERENTIAL  DIAGNOSIS  BETWEEN   THE  VARIOUS 
FORMS  OF  MENINGITIS 

Having  established  the  existence  of  a  meningitis, 
it  remains  for  the  clinician  to  determine,  if  possible, 
that  the  case  belongs  to  the  meningococcic  form.  The 
differentiation  between  this  form  and  tuberculous 
meningitis  is  less  difficult  than  between  the  other 
forms  of  acute  suppurative  meningitis. 

Tuberculous  Meningitis. — A  tuberculous  f  amity 
history  or  one  of  close  contact  with  a  tuberculous 
individual  is  of  considerable  aid  in  the  diagnosis,  but 
its  importance  should  not  be  over-estimated.  Of 
much  greater  significance  is  the  mode  of  onset.  The 
onset  of  tuberculous  meningitis  is  slow  and  insidious. 
It  usually  begins  with  moderate  headache,  occasional 
vomiting,  and  apathy.  These  symptoms  continue  for 
several  weeks  before  the  more  characteristic  mani- 
festations of  meningeal  involvement  appear.  The 
fever  is  moderate  during  the  greater  part  of  the 
course.  Before  death,  sudden  hyperpyrexia  is  very 
commonly  seen.  There  is  early  emaciation.  The 
abdomen  is  scaphoid  in  shape,  and  obstinate  constipa- 
tion is  the  rule.  The  patients  are  indifferent,  listless, 
and  stuporous.  They  sleep  most  of  the  time,  and  do 
not  seem  to  be  fully  conscious  of  their  surroundings. 
They  are  less  disturbed  by  the  physician's  examina- 


DIFFERENTIAL  DIAGNOSIS  221 

tion.  Photophobia  is  very  frequent,  whereas  in 
meningococcus  meningitis  true  photophobia  (i.e.,  due 
purely  to  light  and  not  to  attempts  at  active  retrac- 
tion of  the  eyelids)  is  very  unusual.  The  pulse  is 
usually  slower  and  more  noticeably  irregular.  Slow, 
irregular,  and  sighing  respirations  appear  at  a  more 
early  stage  of  the  disease.  Alternate  flushing  and 
pallor  of  the  face  is  more  often  seen.  In  young 
infants  there  is  marked  bulging  of  the  fontanelle 
early  in  the  disease.  In  older  children  the  Macewen 
sign  is  usually  pronounced.  Transitory  palsies  of 
the  cranial  nerves,  such  as  irregularity  of  the  pupils, 
ocular  muscles  paralysis,  and  facial  paralysis,  are 
very  frequent.  Though  these  symptoms  are  also 
quite  common  in  meningococcus  meningitis,  they  are 
usually  less  pronounced.  Herpes  is  extremely  rare 
in  the  tuberculous  meningitis;  eruptions  and  joint 
disease  are  never  seen.  The  rigidity  of  the  neck  and 
Kernig  sign  are  less  pronounced,  while  retraction  of 
the  head  and  opisthotonus  are  practically  never  ob- 
served. The  deep  reflexes  are  irregular.  Usually 
exaggerated  at  the  onset,  they  are,  as  a  rule,  lost  at 
an  advanced  stage  of  the  disease.  The  Babinski  re- 
flex occurs  in  a  larger  proportion  of  cases.  The 
cutaneous  reaction  of  v.  Pirquet  is  at  times  of  great 
value.  It  is  often  negative  at  an  advanced  stage  of 
the   disease.     The  presence  of  choroid  tubercles   is 


222       MENINGOCOCCUS  MENINGITIS 

pathognomonic.  Unfortunately,  they  are  present  in 
only  a  small  number  of  the  cases.  There  is  moderate 
leucocytosis.  It  is  important  to  bear  in  mind  that  in 
infancy  tuberculous  meningitis  may  run  an  acute 
course,  being  accompanied  by  high  fever  and  gastro- 
intestinal disturbances.  In  adults  the  disease  is  occa- 
sionally very  atypical  and  the  differentiation  between 
the  two  diseases  a  matter  of  extreme  difficulty. 

Acute  Suppurative  Meningitides. — A  great  vari- 
ety of  organisms  are  capable  of  producing  acute 
inflammation  of  the  meninges.  The  most  important 
of  these  are  the  pneumococcus,  streptococcus,  staphy- 
lococcus, influenza  bacillus,  typhoid  bacillus,  and 
bacillus  coli.  The  differentiation  from  meningo- 
coccus meningitis  is  often  impossible  without  lumbar 
puncture.  In  otitic  meningitis  the  history  of  ear  dis- 
charge followed  by  mastoid  involvement  is  very 
significant.  The  course  is  more  insidious  but  pro- 
gressive. Facial  and  motor  oculi  paralyses  and  uni- 
lateral labyrinthine  disturbances  are  very  common. 
The  duration  of  an  acute  meningitis  is  of  some  diag- 
nostic importance.  A  case  that  has  lasted  more  than 
a  week  is  likely  to  be  of  meningococcic  origin. 

The  other  forms  of  acute  meningitis  are  usually 
fatal  within  a  week  from  the  onset.  In  pneumo- 
coccus meningitis  the  meninges  of  the  spinal  cord  and 
nerves  are  less  often  affected,  so  that  rigidity  of  the 


DIFFERENTIAL  DIAGNOSIS  223 

neck  is  less  common  and  involvement  of  the  cranial 
nerves  and  spinal-nerve  roots  less  frequent.  Holt 
has  called  attention  to  the  fact  that,  on  account  of  the 
occasional  localization  of  the  inflammatory  process, 
the  pneumococcus  may  not  be  demonstrable  in  the 
cerebrospinal  fluid.  Acute  meningitis  occurring  as  a 
complication  of  an  acute  infectious  disease,  as  pneu- 
monia, influenza,  or  typhoid,  can  usually  be  dis- 
tinguished from  meningococcus  meningitis  by  finding 
evidence  of  the  existence  of  the  primary  disease. 

Aseptic  Meningitis. — In  disease  of  the  cranial 
bones  we  occasionally  encounter  a  purulent  menin- 
gitis due  to  irritation  in  which  the  fluid  is  free  from 
bacteria.  It  is  also  well  to  bear  in  mind  that  very 
occasionally  the  development  of  a  sterile  purulent 
exudate  takes  place  after  a  lumbar  puncture  or  the 
injection  of  serum  in  non-meningococcic  cases. 

Bibliography 

(Chapters  XII  and  XIII) 

Gocppcrt:    Ergeb.  d.  Inner  Med.  u.  Kindk.,  1909,  iv,  165. 
Koplik:     Amer.  Jour.  Med.  Sciences,  1911,  cxli,  788. 
Zabel:    Mitth.  aus  d.  Grenz.  derMed.  u.  Chir.,  1911,  xxv,  211. 
Remlinger:    Gaz.  des  Hop.,  1911,  lxxxiv,  1125. 
Dubois:    Jour.  Amor.  Med.  Assn.,  1913,  lx,  820. 


CHAPTER  XIV 

Laboratory  Diagnosis 

The  Cerebrospinal  Fluid. — As  has  been  previ- 
ously stated,  the  final  establishment  of  the  etiologic 
diagnosis  is  based  upon  the  study  of  the  cerebrospinal 
fluid  in  the  laboratory.  No  matter  how  certain  the 
diagnosis  is  otherwise,  its  confirmation  by  laboratory 
investigation  of  the  fluid  is  practically  always  indis- 
pensable. 

The  data  yielded  by  the  examination  of  the 
cerebrospinal  fluid  in  the  normal  condition  and  in  a 
number  of  meningeal  and  cerebral  disturbances  is 
given  in  the  table  opposite,  which  is  adapted  from 
Pfaundler's  article  in  "  The  Diseases  of  Children," 
by  Pfaundler  and  Schlossmann. 

The  differential  diagnosis  between  the  inflamma- 
tory exudates  occurring  in  meningitis  and  the  fluid 
found  in  normal  conditions  (i.e.,,  normal  as  regards 
the  meninges  and  central  nervous  system),  in  menin- 
gism,  and  various  other  cerebral  conditions  is  made 
by  estimation  of  the  pressure  of  the  fluid,  the  macro- 
scopic appearance,  the  gross  fibrin  contents,  the  pro- 
tein and  globulin  contents,  the  degree  of  reduction 
by  potassium  permanganate,  the  cytological  and  the 
bacteriological  features. 

224 


marks  the  upper  limit  of  the  puncture — namely,  the  horizontal  line  joining  the 
ail  inserts  a  sterile  needle  about  1  mm.  wide  and  fitted  with  a  stylet,  horizon- 
of  the  manometer  tube  is  attached  to  the  needle.  The  pressure  during  quite 
>e  materially  reduced  below  normal.     The  wound  is  closed  by  adhesive  plaster. 


tional  neuro- 

S^lTiL™  'Sinus  thrombosis, 
ysms,  tetany,) 

chorea). 


lly  increased. 


hange. 


Often     increased. 


Usually  tinted 
with  blood;  of- 
ten brownish- 
green. 


Sedimentation  of 
disintegrated 
blood  masses 
(old  blood)  no 
coagulation. 


Other  pathological  conditions  and  generally 
suggestive  symptoms. 


Rapid  sinking  of  the  pressure  after  drawing 
a  little  fluid,  with  occlusion  of  communica- 
tion to  the  cerebral  region  of  dissemination 
of  the  fluid;  pressure  zero  at  "punctio 
sicca"  (dry  tap).t  Normal  or  low  pressure 
with  good  cardiac  function  excludes  exuda- 
tive affections. 


Bloody  at  puncture  (unchanged  appearance 
of  elements,  gradual  decrease  of  blood  con- 
tents, in  various  portions  during  voiding, 
strong  tendency  to  coagulation),  in  hemor- 
rhagic pachymeningitis,  cerebral  and  men- 
ingeal hemorrhages,  basal  fractures,  in 
(birth)  trauma  (old  blood  discolored,  cor- 
puscles disintegrate,  coagulability  absent). 


jnuclear  and 
nuclear  cells 


Slightly  increased 
lymphocytes. 


A  few  lymphocytes  are  also  found  in  cerebral 
scleroses,  poliomyelitis,  syphilitic  menin- 
gitis, otitis  interna,  whooping-cough,  etc 


Often    somewhat 
increased. 


A.  greater  than  0.1  per  cent,  only  in  exuda- 
tions or  tumors. 

A.  greater  than  0.5  per  cent,  only  in  tubercu- 
lous and  suppurative  meningitis  (aside  from 
the  cases  with  puncture  hemorrhage). 


demonstra- 


Sugar  demonstra- 
ble. 


Absence  of  sugar;  usually  exudation. 


Mixed  infections  not  seldom  in  tuberculous 
and  cerebrospinal  meningitis.  In  athrepsia 
often  intestinal  bacteria. 


X< 


»°  *ie  avoided.    The  speed  at  which  the  fluid  is  voided  is  no  criterion  for  the 


tv  *°  antity  present. 


Tccknie  of  Lumbar  Pun< 


a  and  at  the  medium  phase  of  r 


t  the  edge  of  the  table,  where  i 


,  standing  at  the  patie 


Symptomatology  of  Fluid  Obtained  by  Lumbar  Puncture  (Pfaundler  and  Schlossmann). 
i  a  bent-forward  position.  The  a 


;'  the  needle  is  suddenly  diminished.     The  atylet  having  I 
;o  rise.*   Then  the  fluid  is  slowly  drawn  off  into  aterile  gla 


rithdrawn,  the  headpiece  of  t 


>er  limit'  of  the  puncture— 
irile  needle  about  1  mm. 
:  tube  is  attached  u.  ■■ 


t  be  materially  reduced  below  n 


nd  is  closed  by  adhesi 


■ — 

Normal  finding. 

Tuberculous  meningitis. 

Cerebrospinal  meningitia. 

Suppurative 
meningitis. 

Serous 
ingitis. 

Chronic    internal 

hydrocephalus 

(acquired). 

Cerebral  tumor. 

Meningismue    (in 
reflex  irritation). 

Functional  neuro- 
ses (epilepsy  in 
paroxysms,  tetany 
chorea). 

Sinus  thrombosis. 

Infants. 

Older 

children. 

State  of  irritation 
and    pressure. 

State  of 
paralysis. 

Acute   proceaa. 

mS'si™. 

suggestive  symptoms. 

before    drawing 
fluid;     medium 
phase    of    respi- 
ration;   patient 
sitting. 

About 
10-20. 

About 
15-25 
(to  35). 

Always   consider- 
ably   increased, 

and    beyond, 

oessive  (100  mm. 

Not  increased. . . . 

Usually  increased 
but    not    exces- 
sively (up  to  50 

Normal . . 

In  the  beginning 
and  at  the   cli- 
max usually  in- 
creased   up     to 
about  40   mm.; 

Nearly  al- 

considerably  in- 
oreaeed  (to 
about  60  mm.). 

Behavior    vary- 

considerable  in- 

In  the  average, 
slightly  increas- 

about  45  mm. 

Usually  increased 

Often     increased. 

Rapid  sinking  of  the  pressure  after  drawing 
a  little  fluid,  with  occlusion  of  communica- 
tion to  the  cerebral  region  ol  <li^eiYiinai!.-.n 

sicca"  (dry  tap). J     Normal  or  low  pressure 

tive  affections. 

Clear     as     water; 

the   finest   "sun 
apecka;"  color- 
yellowish  tint  in 
a  thick  layer. 

Often  clear  (%  of 
the  cases);  oth- 

ated    by    finest 
specks,     glitter- 
ing in   the  sun- 
light. 

Slightly     dense, 
grayish  -white 
turbidity;    very 
rarely    purulent 

Always    turbid; 

ed   with   blood; 
seldom  purulent. 

Almost  (or 
clear. 

Usually  consider- 

white  or  grayish- 
yellow  turbidity 
in  yellow-tinted 
fluid  (only  quite 
exceptionally 

Clear,  col- 
orless. 

Nearly  always 
perfectly  clear. 

Varying,    usually 

Usually  clear;  on 
closer  inspection 
with  light  fall- 
ing through  and 

specks  recogniz- 
able. 

Usually  tinted 
with  blood;  of- 
ten    brownish- 

Bloody  at  puncture  (unchanged  appearance 
of  elements,  gradual  decrease  of  blood  con- 
tents, in  various  portions  during  voiding, 
strong  tendency  to  coagulation),  in  hemor- 
rhagic pachymeningitis,  cerebral  and  men- 
ingeal hemorrhages,  basal  fractures,  in 
(birth)  trauma  (old  blood  discolored,  cor- 
puscles disintegrate,  coagulability-  ^b^nn. 

pearance  of  the 

Change  of  fluid  on 

Very  often  forma- 

web-like   c  o  ag  - 
ulum;   seldom 

cloudy  flakes. 

Sedimentation  of 
pus,    frequently 
formation  of  fi- 

No  ohange 

Sedimentation   of 
oreamy  pus  and 
net  formation. 

No    coag- 
ulation. 

Exceptionally  co- 
agulation in  net 

Sometimes  occur- 
rence of  a  sedi- 
ment which  is 
JuBt  perceptible; 
no  coagulation. 

Sedimentation  of 

disintegrated 

(old  blood)  no 
coagulation. 

Character  of  cellu- 
obtained  by  sed- 

Exceedingly     few 
lymphocytes,  er- 
ythrocytes,   and 
endothclia;      no 
more  than  about 
6  cells  per  o.mm. 

Abundant  lymphocytes  and  polynu- 
olear   leucocytes;   the  former  often 
vastly  preponderating,  the  latter  in- 
creased in  mixed  infection. 

Polynuclear     cella     predomi- 
nating, lymphocytes  in  the 
stage  of  advanced  healing, 
possibly  erythrocytes, 

Polynuclear    cells 
predominating. 

Dial,   or 
lympho- 

w  h  a  t 

abundant 

Frequently  in- 
creased    uninu- 

nuolear   cells; 

tides  (?) 

Slightly  increased 

and  rarely  poly- 
nuclear leu  oo- 

Mononuclear  and 
polynuclear  cells. 

Slightly  increased 

lymphocytes. 

A  few  lymphocytes  are  also  found  in  cerebral 
scleroses,  poliomyelitis,  syphilitic  menin- 
gitis, otitis  interna,  whooping-cough,  etc. 

Albuminous     con- 
tents of  the  fluid 

ed  after  Brand- 

0.02  per  cent.  =or 
<  A.  <0.05   per 
cent  (globulin). 

Always  increased;  1  Average  about  0.4 
0.1-0.7  per  cent. ;      per  cent. 
average      about 
0.2  per  cent.         | 

Albuminous    contents    gradually    in- 
creasing in  the  course  of  the  entire 
process. 

Varying,  usually 
considerably  in- 
creased. 

Normal. 

Very  considerably 
increased  (up  to 

Average 
equals  or 
is    leas 
than  0.1 
per  cent. 

Nearly     alwaya 

Often  increased, 
exceptionally  up 

Rarely  slightly  in- 
creased. Aver- 
less  than  0.1  per 

Often     somewhat 

A.  greater  than  0.1  per  cent,  only  in  exuda- 

A.  greater  than  0.5  per  cent,  only  in  tuberou- 
lous  and  suppurative  meningitis  (aside  from 
the  oases  with  puncture  hemorrhage). 

Sugar  contents  of 
fluid    (Worm- 
Muller's  test). 

Sugar  always  de- 
monstrable. 

Sugar  teats  nearly  always  negative,  even  after  previous  elimination 
of  albumin. 

ly  always  ncga- 

previous    elimi- 
nation of  alb'n. 

Sugar    of- 

demon- 
etrable. 

Sugar  alwaya  de- 
monstrable. 

Sugar  usually  de- 
monstrable. 

Sugar  demonstra- 
ble. 

Sugar  demonstra- 
ble. 

Sugar  demonatra- 
ble. 

Absence  of  sugar;  usually  exudation. 

In  30-50  per  cent. 
of   the    cases 
tubercle    bacilli 
demonstrable. 

Pneumococoi, 

staphylococci, 

oocci;    typhoid, 
influenza,      and 
colon  bacilli. 

Wi  th  tubercles, 
poaaible  tuber- 
cle bacilli. 

In  infections  var- 
ious bacteria 
were  found, 
without  inflam- 
matory reaction 
of  the  meninges. 

of  fluid. 

the  caBes  tuber- 
cle bacilli;  post- 
mortem always. 

ingococcus  ot  Weionselbaum 
and  kindred  types. 

and  cerebrospinal  meningitis.  In  athrepsia 

Creamy  pus  with 

Increased 

with  clear 
fluid. 

Increased  pressure 
with    otherwise 
normal   condi- 

A 

istiofindings.g 

ole  bacmie.331Ve  P 

ressure,  and  tuber- 

punctures;     pus 

-cells     and 

a  pressure,  in  which  before,  or  during  the  procedure  considerable  quantities  of  fluid  are  drawn,  b 


a  permeability  of  the 


,        t... .  „ . foramen  of  Magendie .         .  .. 

,  specific  gravity,  toxicity,  and  oflmotio  pressure  of  the  cerebrospinal  fluid  are  of 


i  children).    By  the 

Staining:  triacid,  azur< 
r;  also  in  hydrocephalus . 
o  particular  practical  importance.    The  quantity  voided 


i  of  mercury  r. 

•t  eoain-hasmat 

l  jelly-like  exudate,  : 


ira  this  drawb  IcaHn  bo  avoided.    The  speed  e 

cerebral  hypertrophy,  etc. 

is  no  criterion  for  the  quantity  present. 


i  the  fluid  is  voided  i 


LABORATORY  DIAGNOSIS  225 

In  meningeal  irritation  and  inflammation  there  is 
usually  found  an  increase  in  the  pressure  of  the 
cerebrospinal  fluid.  As  a  rule,  it  is  more  marked  in 
the  latter  than  in  the  former.  The  method  of  esti- 
mating the  pressure  has  been  discussed  in  a  previous 
chapter.  In  inflammatory  fluids  there  is  usually  some 
degree  of  turbidity  or  opalescence.  While  normal 
fluid  has  the  appearance  of  absolutely  clear  water, 
the  fluid  in  inflammatory  conditions  of  the  meninges, 
even  when  apparently  quite  clear,  will  usually  reveal 
the  presence  of  small  dancing  particles  when  a  ray  of 
light  is  passed  through  the  column  of  fluid. 

The  gross  fibrin  content  which  becomes  apparent 
upon  standing  is  usually  increased  in  all  forms  of 
meningitis.  The  normal  fluid  contains  very  little 
fibrin. 

The  estimation  of  the  protein  content  is  made 
either  by  the  acetic  acid  test  of  Moritz  (addition  of  a 
few  drops  of  5  per  cent,  acetic  acid  to  2  cubic  centi- 
metres of  fluid)  or  by  the  nitric  acid  ring  test.  Only 
a  trace  of  albumin  is  present  in  normal  fluid  and  in 
the  fluid  in  meningism.  It  varies  considerably  in  the 
various  forms  of  meningitis,  being  less  abundant  in 
tuberculous  meningitis.  The  globulin  content  can  be 
estimated  by  the  tests  of  Nonne  and  Apelt,  Xoguchi, 
and  Braun  and  Husler. 

Nonne  and  Apelt's  Test. — Phase  I:  Equal  parts 

15 


226       MENINGOCOCCUS  MENINGITIS 

of  cerebrospinal  fluid  and  a  heat-saturated  solution  of 
ammonium  sulphate  are  mixed  in  the  cold.  The  re- 
action is  considered  positiA^e  if  opalescence  occurs 
within  three  minutes.  This  occurs  only  when  there  is 
an  increase  of  globulin,  and  is  seen  only  in  patho- 
logical specimens. 

Phase  II:  The  mixture  is  filtered  and  the  filtrate 
is  then  boiled  after  the  addition  of  a  drop  of  acetic 
acid.  A  precipitate  indicates  the  presence  of  albu- 
mins.   A  positive  Phase  II  is  seen  in  normal  fluids. 

Noguchi  Test. — This  is  a  simple  and  delicate  test: 
0.1  or  0.2  cubic  centimetre  of  cerebrospinal  fluid  is 
mixed  with  0.5  cubic  centimetre  of  10  per  cent,  solu- 
tion of  butyric  acid  in  normal  salt  solution.  The 
mixture  is  then  heated  over  a  flame  for  a  brief  period. 
0.1  cubic  centimetre  of  normal  sodium  hydrate  solu- 
tion is  then  quickly  added  to  the  heated  mixture  and 
the  whole  boiled  once  more.  A  positive  reaction  is 
shown  by  the  formation  of  a  granular  or  flocculent 
precipitate  within  two  hours.  In  normal  fluid  at  most 
only  a  slight  opalescence  or  turbidity  occurs. 

Braun  and  Husler  Test. — This  is  a  modification 
of  the  test  of  Sachs  and  Altmann,  and  is  carried  out 
as  follows: 

To  1  cubic  centimetre  of  cerebrospinal  fluid  there 
is  added  slowly,  1  cubic  centimetre  at  a  time,  n/300 
HC1,  the  mixture  being  constantly  shaken.     When 


LABORATORY  DIAGNOSIS  227 

the  test  is  positive,  a  precipitate  forms  within  one- 
half  hour. 

A  quantitative  albumin  estimation  may  be  made 
by  the  use  of  the  Esbach  reagent. 

Mayerhofer  has  shown  that  there  is  a  marked 
difference  between  normal  and  inflammatory  fluid 
in  the  degree  of  reduction  of  potassium  permanganate 
when  boiled  in  an  acid  medium.  In  meningitis  the 
index  of  reduction  is  high,  from  2  to  8.  As  it  usually 
drops  after  the  injection  of  antimeningitis  serum, 
this  test  may  be  of  some  value  as  an  indication  of 
beginning  recovery. 

Three  methods  are  in  use  for  the  examination  of 
the  cells  of  the  cerebrospinal  fluid: 

1.  The  centrifuge  method,  developed  by  Widal, 
Sicard,  and  Ravant. 

2.  The  cell-chamber  method,  introduced  by 
Laignel-Lavastina  and  modified  by  Fuchs  and 
Rosenthal. 

3.  The  microtome  method,  introduced  by 
Alzgeimer. 

As  pointed  out  by  Bybee  and  Lorenz,  the  centri- 
fuge method  is  inaccurate,  owing  to  the  fact  that  the 
cells  become  clumped  and  adhere  to  the  bottom  and 
sides  of  the  centrifuge  tube.  Moerover,  it  does  not 
permit  of  an  accurate  quantitative  estimation  of  the 
cells,  on  account  of  variation  in  the  size  of  the  drops, 


228       MENINGOCOCCUS  MENINGITIS 

as  well  as  the  area  covered  by  each  drop.  The  micro- 
tome method  of  Alzheimer  is  too  slow  and  cumber- 
some. Bybee  and  Lorenz  advise  a  modification  of 
the  Fuchs-Rosenthal  cell-chamber  method.  They 
employ  a  red-cell  counter,  and  a  stain  composed  of 

Methyl  violet    0.1 

Glacial  acetic  acid    2.0 

Distilled  water  up  to 50.0 

For  ordinary  clinical  purposes,  however,  the  use  of 
the  centrifuge  and  Hastings  or  Jenner  stain  gives 
sufficiently  good  results. 

The  cytologic  examination  of  the  cerebrospinal 
fluid  yields  extremely  valuable  results  (Fig.  28). 
An  increase  in  the  cellular  elements  is  present  in  all 
forms  of  inflammation  of  the  meninges.  In  the  puru- 
lent cases  there  is  a  preponderance  of  polymorphonu- 
clear cells  (80  to  100  per  cent.),  whereas  in  tubercu- 
lous meningitis  the  lymphocytes  are  greatly  in  excess 
(70  to  100  per  cent.).  Very  recently,  however,  we 
observed  a  case  of  tuberculous  meningitis  (proved  by 
finding  the  tubercle  bacillus  in  the  cerebrospinal 
fluid)  in  which  the  cells  were  exclusively  of  the  poly- 
morphonuclear types.  On  the  other  hand,  it  is  im- 
portant to  bear  in  mind  that  in  the  later  stages  of 
meningococcus  meningitis  and  throughout  the  whole 
course  of  the  posterior  basic  cases  a  relative  lympho- 


I  [o    28      A,  cytology  of  epidemic  cerebrospinal  meningitis.    Polynuclear  cells     Menin- 
igj  ..i  tuberculous  meningitis  (specimen  of  Dr.  E.  P.  Bernstein).     Mono- 
nuclear rclls      •  »!i«-  i  ii1iiti-Ic  liai'illus. 


LABORATORY  DIAGNOSIS  229 

cytosis  is  present.  A  diagnosis  can,  however,  rarely 
be  definitely  based  upon  the  cytological  character  of 
the  fluid  alone,  without  the  demonstration  of  the 
organisms  producing  the  infection. 

Absolute  certainty  of  etiologic  diagnosis  is  attain- 
able only  by  finding  either  microscopically  or  cultur- 
ally the  meningococcus  in  the  cerebrospinal  fluid.  In 
the  vast  majority  of  the  acute  cases,  we  are  able  to  do 
this  at  the  first  examination  if  we  examine  the  fluid 
by  the  Gram  stain  and  make  cultures  with  sufficient 
quantities  of  fluid  as  soon  as  possible  after  its  with- 
drawal. 

It  is  desirable  to  make  cultures  in  all  cases,  as 
occasionally  these  show  the  positive  growth  when  the 
smears  fail  to  reveal  the  presence  of  the  meningo- 
coccus. For  their  microscopical  identification  it  is, 
however,  usually  sufficient  if  we  can  demonstrate  the 
presence  in  the  smears  of  Gram-negative,  intra-  and 
extracellular,  hemispherical  diplococci.  In  chronic 
cases  it  is  not  at  all  rare  to  find  the  fluid  sterile  micro- 
scopically as  well  as  culturally.  In  these  cases  the 
diagnosis  must  be  based  upon  the  history  of  sudden 
onset  and  the  clinical  picture  of  the  disease.  Differ- 
entiation from  tuberculous  meningitis  is  usually  not 
difficult  when  the  clinical  features  of  the  disease  are 
carefully  analyzed  and  the  tubercle  bacillus  is  found 
by  long  and  patient  search.    Bernstein  found  tubercle 


230       MENINGOCOCCUS  MENINGITIS 

bacilli  in  98  per  cent,  of  102  cases,  while  Hemenway 
succeeded  in  finding  them  in  135  out  of  137  cases 
examined. 

Precipito-Reaction  of  Vincent  and  Bellot. — While 
the  cerebrospinal  fluid,  in  contrast  to  the  blood,  does 
not,  as  a  rule,  possess  specific  agglutinins,  antibodies, 
bacteriotropins,  or  opsonins  in  more  than  mere  traces, 
Vincent  and  Bellot  have  shown  that  there  is  present  in 
the  cerebrospinal  fluid  of  meningococcus  meningitis 
a  substance  which  forms  a  precipitate  with  anti- 
meningitic  serum.  This  is  probably  an  extract  or 
autolysate  of  the  meningococcus. 

The  test  is  performed  by  adding  from  two  to  five 
drops  of  antimeningitis  serum  to  fifty  and  one 
hundred  drops  of  cerebrospinal  fluid,  which  has  been 
previously  clarified  by  centrifugalization.  These 
mixtures  and  a  control  (containing  fluid  but  no 
serum)  are  placed  in  the  incubator  at  50°  C.  for  eight 
to  fourteen  hours.  If  the  fluid  is  one  derived  from  a 
case  of  meningococcus  meningitis,  the  mixtures  of 
the  fluid  and  serum  become  turbid  or  opalescent, 
while  the  control  remains  clear.  The  test  must  be  per- 
formed immediately  after  the  cerebrospinal  fluid  is 
withdrawn  from  the  spinal  canal.  It  must  not  be 
exposed  to  the  air  or  light  for  any  length  of  time. 
Evaporation  of  the  fluid  while  in  the  incubator  should 
be  prevented  by  the  use  of  a  rubber  stopper.    Occa- 


LABORATORY  DIAGNOSIS  231 

sionally  the  test  first  becomes  positive  after  twenty- 
four  to  thirty-six  hours'  incubation.  This  reaction 
appears  early  in  the  course  of  the  disease,  within 
twelve  hours,  and  persists  for  fifteen  to  twenty  days. 
In  61  normal  subjects,  Vincent  and  Bellot  found  the 
reaction  negative,  while  in  all  of  32  cases  of  menin- 
gococcus meningitis  it  was  positive.  Their  observa- 
tions were  confirmed  by  Louis  and  Salebert.  The 
test  is  best  performed  on  the  first  lumbar  puncture, 
as  it  is  conceivable  that  the  injection  of  serum  might 
lead  to  precipitation  within  the  canal  and  consequent 
exhaustion  of  the  precipitable  body.  In  some  cases 
Letulle  and  Legane  found  that  the  control  became 
spontaneously  turbid,  and  the  test  was  then  incon- 
clusive. In  a  few  cases  a  positive  reaction  has  been 
present  in  pneumococcus  meningitis.  This  test  may 
prove  of  great  value  in  those  cases  where  cerebro- 
spinal fluid  is  apparently  sterile.  At  any  rate,  the 
test  is  readily  performed  and  deserves  to  be  more 
generally  recognized  in  this  country. 

Presence  of  Complement. — Weil  and  Kafka  have 
demonstrated  by  hemolytic  tests  the  presence  of  both 
complement  and  amboceptor  in  the  cerebrospinal 
fluid. 

Complement  Fixation. — Bruynoghe  found  fixa- 
tion of  complement  by  specific  antigen  in  12  cases  of 
meningococci  meningitis. 


232       MENINGOCOCCUS  MENINGITIS 

Sodium  Taurocholate  Test. — Danielopolu  found 
that  the  normal  inhibition  of  cerebrospinal  fluid  on 
the  hemolytic  action  of  sodium  taurocholate  on  dog's 
blood  is  greatly  increased  in  meningitis.  He  claims 
that  this  test  is  positive  long  before  there  is  a  change 
in  the  cytology  of  the  fluid. 

Animal  Inoculation. — By  inoculating  0.5  to  0.75 
cubic  centimetre  of  cerebrospinal  fluid  in  the  lumbar 
subarachnoid  space  of  small  guinea-pigs,  v.  Grysez 
produced  death  in  from  two  to  twenty-four  hours.  A 
reduction  of  temperature  of  4°  to  8°  C.  occurred 
within  an  interval  varying  from  ten  minutes  to 
twenty-four  hours.  He  considers  the  lowering  of  the 
temperature  characteristic,  and  advises  the  use  of 
this  test  as  a  valuable  aid  in  the  diagnosis  of  fluids 
that  do  not  reveal  the  presence  of  the  meningococcus. 

THE  BLOOD 

The  examination  of  the  blood  often  yields  results 
which  are  of  great  aid  in  the  diagnosis.  The  presence 
of  a  well-marked  polymorphonuclear  leucocytosis, 
especially  in  the  acute  stage,  serves  to  differentiate 
the  disease  from  a  number  of  other  affections  which 
are  characterized  by  a  normal  leucocyte  count  or 
leucopamia,  such  as  typhoid  fever  and  anterior 
poliomyelitis. 

Agglutination. — The  agglutinative  properties  of 


LABORATORY  DIAGNOSIS  233 

the  serum  in  meningococcus  meningitis  are  rather  in- 
constant. Specific  agglutinins  are  rarely  demon- 
strable in  the  first  few  days  of  the  disease.  At  the 
end  of  the  first  week  the  agglutination  reaction  is 
almost  always  positive.  It  disappears  rapidly,  and  in 
convalescence  is  practically  always  absent.  It  is  fre- 
quently present  in  the  mild  and  abortive  types,  but 
usually  not  demonstrable  in  the  chronic  cases.  It  is 
naturally  not  to  be  expected  in  the  fulminating  type 
of  the  disease,  as  death  takes  place  within  the  first 
forty-eight  hours.  It  is  of  especial  value  in  those 
cases  in  which  the  meningococcus  for  one  reason  or 
another  cannot  be  found  in  the  cerebrospinal  fluid. 
In  addition,  the  test  may  serve  to  clear  up  the  nature 
of  those  cases  in  which  the  mild  character  of  the 
symptoms  does  not  justify  the  performance  of  a 
lumbar  puncture.  On  account  of  its  comparatively 
late  appearance,  a  diagnosis  will  usually  have  been 
made  before  this  test  is  employed. 

Technic. — A  loopful  of  a  culture  of  the  organism 
which  has  previously  been  tested  as  to  its  agglutin- 
ability  is  thoroughly  shaken  in  each  tube  of  a  series 
containing  one  cubic  centimetre  of  serum  diluted  in 
1/10,  1/25,  1/50,  1/100,  1/200,  1/400,  etc.,  with  salt 
solution.  These  tubes,  with  two  controls  each,  one 
of  serum  alone  and  the  other  of  a  suspension  of  the 
culture  in  salt  solution,  are  then  placed  in  the  in- 


234       MENINGOCOCCUS  MENINGITIS 

cubator  at  37°  C.  The  results  are  read  off  at  the  end 
of  four,  eight,  and  twenty-four  hours.  A  positive 
reaction  is  indicated  by  the  formation  of  a  visible 
sediment  at  the  bottom  of  the  tube  and  clarification 
of  the  supernatant  fluid.  The  index  of  agglutination 
is  the  highest  dilution  of  the  serum  at  which  such 
sedimentation  still  occurs.  Kutscher  has  shown  that 
at  times  better  results  are  obtained  if  the  tubes  are 
kept  in  the  incubator  at  55°  C. 

Opsonic  Index. — This  reaction  appears  rather  late 
in  the  disease,  so  that  a  diagnosis  will  usually  have 
been  made  before  it  is  employed.  Houston  and 
Rankin  found  a  high  opsonic  index  over  four,  after 
the  sixth  day  of  the  disease.  MacGregor  observed 
the  highest  indices  in  the  second  and  third  weeks  of 
the  disease.  Davis  found  that  the  index  was  incon- 
stant, owing  to  variations  in  the  strains  of  menin- 
gococci. Occasionally  it  persisted  for  two  or  three 
weeks  and  ran  parallel  with  agglutinative  reaction. 
Its  absence,  therefore,  does  not  necessarily  exclude 
the  presence  of  meningococcus  meningitis.  When 
present,  however,  it  makes  the  diagnosis  almost  cer- 
tain, as  specific  opsonic  action  on  the  meningococcus 
is  not  seen  in  any  other  condition.  The  technic  is 
very  difficult,  and  if  the  test  is  to  be  of  any  value  it 
must  be  carried  out  by  one  who  is  thoroughly  versed 
in  opsonic  determinations. 


LABORATORY  DIAGNOSIS  235 

Complement  Fixation. — Positive  results  with  this 
method  have  been  obtained  by  Cohen  and  Schumann, 
but  its  diagnostic  value  is  not  as  yet  definitely  deter- 
mined. 

Bactericidal  Bodies  were  demonstrated  in  the 
blood  by  Davis  and  Dopter  late  in  the  disease. 

Demonstration  of  the  Meningococcus  in  the 
Blood. — A  great  number  of  investigators  have  found 
the  meningococcus  in  the  blood.  The  most  important 
of  these  observations  are  those  of  Elser,  who  in  a 
series  of  41  cases  succeeded  in  isolating  the  menin- 
gococcus from  the  blood  in  11.  But  the  number  of 
organisms  appeared  to  be  small,  as  growth  took  place 
in  only  one  or  at  most  two  of  the  three  culture  flasks 
used.  These  results  indicate  that  in  most  of  the  cases 
a  transient  invasion  of  the  blood  stream  exists  and  not 
a  true  septicaemia. 

BACTERIOLOGICAL  EXAMINATION  OF  THE 
NASOPHARYNX 

We  have  in  the  previous  chapter  seen  how  con- 
stantly the  meningococcus  is  found  in  the  naso- 
pharyngeal secretion  of  patients  during  the  early 
stages  of  the  disease,  and  it  might  therefore  appear 
as  though  the  bacteriological  examination  of  this 
region  should  prove  to  be  of  considerable  aid  in  the 
clinical  diagnosis.    Unfortunately,  its  practical  value 


236       MENINGOCOCCUS  MENINGITIS 

is  greatly  limited  by  reason  of  the  fact  that  the  technic 
involved  in  the  isolation  of  the  organisms  from  the 
nasopharynx  is  rather  long  and  difficult.  It  can  only 
be  carried  out  in  institutions  that  have  the  proper 
facilities  for  modern  bacteriological  investigations. 

Bibliography 

Davis :    Jour.  Infect.  Diseases,  1905,  ii,  602. 

Houston  and  Rankin:    Brit.  Med.  Jour.,  1907. 

Taylor:    Lancet,  1907,  i,  16. 

Schumann:     Med.  Klinik,  1908. 

Vincent  and  Bellot:    Bull,  et  Mem.  Soc.  Med.  des  Hop.,  1909, 

xxvii,  952. 
Louis:   Compt.  rend.  Soc.  de  Biol.,  1909,  lxvi,  814. 
Letulle  and  Lagane:    Compt.  rend.  Soc.  de  Biol.,  1909,  lxvi, 

758. 
Elser  and  Huntoon:    Jour.  Med.  Research,  1909,  xx,  377. 
Cohen:    La  Presse  Medicale,  1909,  xvii,  791. 
Bruynoghe:     Cent.  f.  Bakt.,  1911,  1  Abt.,  Orig.,  581. 
Pfaundler,  in  Pfaundler  and  Schlossman:     The  Diseases  of 

Children,  Eng.  Trans.,  Phila.,  2d  ed.,  1912,  i,  196-7. 
Danielopolu:    Wien.  klin.  Wochenschr.,  1912,  xxv,  1476. 


CHAPTER  XV 

Prognosis 

The  prognosis  of  meningococcus  meningitis, 
even  since  the  introduction  of  specific  serotherapy, 
remains  a  comparatively  grave  one.  In  general  it 
may  be  stated  that  the  sporadic  form  of  the  disease 
is  less  severe  than  the  epidemic  form.  This  is  well 
shown  by  the  statistics  of  Koplik  at  Mount  Sinai 
Hospital.  In  the  five  years  from  1899  to  1903  in- 
clusive, 21  sporadic  cases  of  the  disease  were  admitted 
to  the  Children's  Service,  of  which  8  died, — i.e.,  a 
mortality  of  38  per  cent.  Deducting  the  cases  below 
two  years  of  age,  there  was  left  a  mortality  of  13  per 
cent.  In  1904  and  1905,  the  two  epidemic  years  in 
New  York  City,  74  cases  were  admitted,  with  a 
mortality  of  50  per  cent.;  of  these  51  cases  were 
above  two  years  of  age,  and  31  per  cent.  died.  We 
thus  see  a  striking  difference  in  the  mortality  be- 
tween epidemic  and  sporadic  cases  under  the  same 
form  of  treatment. 

The  mortality  has  varied  greatly  in  different 
epidemics.  Even  in  the  same  epidemic  some  localities 
exhibit  a  graver  form  of  the  disease  than  others.  The 
severity  of  the  disease  usually  diminishes  toward  the 

237 


238       MENINGOCOCCUS  MENINGITIS 

end  of  an  epidemic.  In  general  we  may  state  that 
the  mortality  in  eases  diagnosed  bacteriologically  and 
not  treated  by  specific  serum  varies  from  50  to  75 
per  cent. 

Indeed,  in  the  recent  epidemics  in  Germany,  the 
United  States,  England,  and  France,  the  mortality 
rate  approached  or  even  passed  the  upper  of  the  two 
percentage  rates  given  above.  Thus,  in  New  York 
City  in  the  epidemic  of  1904-1905,  there  were  about 
4000  cases  with  3429  deaths, — i.e.,  a  mortality  of 
73.5  per  cent.  Chase,  in  Akron,  Ohio,  had  a  mortality 
of  90  per  cent.  Ladd  in  the  same  State  had  a  mortal- 
hy  of  80  per  cent.;  while  among  the  patients  of 
Sladen,  at  Baltimore,  the  mortality  was  64  per  cent. 
In  1907  Robb,  in  Belfast,  treated  275  cases,  of  whom 
199  died, — that  is,  a  mortality  of  72.13  per  cent.  Of 
108  patients  treated  by  Ker,  in  Edinburgh,  80.5  per 
cent.  died. 

We  can  not  attach  too  much  importance  to  the 
statistics  of  the  earlier  authors,  which  is  summarized 
by  Hirsch,  in  his  monograph,  who  finds  the  average 
mortality  in  the  epidemics  collated  by  him  to  be  37 
per  cent.,  on  account  of  the  lack  of  bacteriological 
proof  of  the  nature  of  the  disease.  The  reduction  in 
mortality  since  the  introduction  of  serotherapy  will 
be  statistically  shown  in  the  chapter  on  Treatment. 


PROGNOSIS  239 

Individual  Prognosis. — There  are  few  infectious 
diseases  in  which  the  ultimate  prognosis  of  any 
individual  case  is  so  surrounded  by  uncertainties  as  it 
is  in  meningococcus  meningitis.  Patients  who  are 
apparently  in  an  extremely  grave  condition  recover; 
and,  on  the  other  hand,  as  long  as  there  is  any  fever  it 
can  not  be  foretold  with  certainty  that  recovery  will 
surely  take  place.  This  is  due  to  the  fact  that  re- 
lapses are  so  common  in  this  disease.  If  the  pulse  is 
over  100,  even  though  the  temperature  has  been 
normal  for  some  time,  the  occurrence  of  a  relapse  is 
not  unlikely.  Similarly,  as  long  as  the  Kernig  sign 
persists,  we  can  not  be  sure  that  the  patient  has 
escaped  the  danger  of  a  relapse.  According  to  Alt- 
man,  we  may  confidently  expect  recovery  if  the  pulse 
is  regular  and  of  normal  frequency  and  the  tempera- 
ture has  been  normal  for  fourteen  days. 

Factors  Influencing  the  Prognosis. — The  previ- 
ous condition  of  the  patient  plays  a  comparatively 
unimportant  role.  Patients  in  robust  health  previous 
to  the  onset  of  the  disease  may  die,  while  delicate 
patients  recover.  Chronic  alcoholism  is  considered 
by  most  authors  a  factor  which  seriously  compromises 
the  patient's  chance  of  recovery. 

Age. — The  age  of  the  patient  is  a  factor  of  the 
greatest  importance  in  the  final  outcome  of  the  dis- 
ease.    Its  influence  is  well  shown  in  the  following 


240       MENINGOCOCCUS  MENINGITIS 

table,  in  which  the  mortality  of  211  cases  treated  at 
the  Mount  Sinai  Hospital  from  1901  to  1906  is 
given. 


1  year 

2  years 
3-5  years .  . 
5-10  years . 
10-15  years 
15-20  years 
20-30  years 
30-40  years 
40-50  years 
50-60  years 


Cured. 

Unimproved. 

Died. 

10 

5 

23 

2 

2 

13 

22 

2 

15 

32 

0 

21 

14 

0 

9 

12 

0 

11 

6 

0 

5 

3 

0 

5 

1 

0 

2 

0 

0 

5 

Percentage  of 
unimproved 

cases 
and  deaths. 


74 
88 
41 
40 
39 
48 
45 
63 
67 
100 


Early  Diagnosis  and  Application  of  Serum  Treat- 
ment.— By  far  the  most  important  prognostic  factor 
is  the  time  of  the  first  application  of  the  serum.  The 
tables  given  in  the  chapter  on  Treatment  make  this 
fact  very  evident.  Early  treatment  presupposes 
early  diagnosis.  As  it  is  a  matter  of  considerable 
difficulty  in  infancy,  this  fact  accounts  in  part  for  the 
high  mortality  at  this  period  of  life,  even  under  serum 
treatment. 

Symptoms  Indicative  of  a  Grave  Condition. — The 
presence  of  one  or  more  of  the  following  symptoms 
indicates  that  the  case  in  hand  is  of  a  grave  nature: 
early  and  persistent  coma  with  loss  of  sphincteric  con- 
trol ;  violent  delirium ;  repeated  convulsions,  especially 


PROGNOSIS  241 

if  appearing  late  in  the  disease  (in  infants  convulsions 
have  not  the  same  grave  significance  as  in  older  chil- 
dren and  adults)  ;  very  rapid  and  small  pulse;  re- 
spirations above  36  in  adults  (this  usually  indicates 
the  presence  of  pulmonary  complications)  ;  persistent 
vomiting  or  diarrhoea;  profuse  purpura  within  the 
first  thirty-six  hours;  hemorrhages  from  the  mucous 
membranes;  complete  insomnia;  general  tremor; 
general  relaxation. 

The  occurrence  of  the  following  complications 
seriously  compromises  the  patients'  chance  of  re- 
covery: pneumonia;  pleurisy,  especially  if  purulent  in 
character;  pericarditis,  which  is  usually  purulent; 
severe  hydrocephalus. 

On  the  other  hand,  the  following  features  of  the 
disease  are  not  of  great  value  in  the  prediction  of  the 
outcome  of  an  individual  case:  the  character  of  the 
onset,  the  type  and  height  of  the  temperature,  the 
intensity  of  the  headache,  the  degree  of  rigidity,  the 
emaciation,  the  irregularity  of  the  pulse,  herpes, 
petechia?,  and  joint  involvement. 

Prognosis  as  to  Complete  Recovery. — Since  the 
early  and  systematic  employment  of  the  specific 
serum,  most  of  the  cases  that  recover  at  all  regain 
completely  their  previous  good  health.  In  some  cases, 
however,  there  is  temporary  persistence  of  rigidity, 
awkwardness  in  gait  and  movements  of  the  arms,  loss 

16 


242       MENINGOCOCCUS  MENINGITIS 

of  the  tendon  reflexes,  irregularity  of  the  pulse,  and 
change  in  character.  These  symptoms  in  most  cases 
ultimately  disappear  completely.  Chronic  hydro- 
cephalus, if  severe,  is  usually  incurable.  Slight 
degrees  of  hydrocephalus,  on  the  other  hand,  usually 
disappear  without  leaving  any  trace  of  its  previous 
existence.  Paralyses  do  not,  as  a  rule,  persist  unless 
they  are  due  to  cerebral  hemorrhage  or  involvement 
of  the  ganglion-cells  of  the  anterior  horn.  Deafness 
and  blindness  are  usually  permanent.  Psychic  dis- 
turbances, such  as  irritability,  sudden  unprovoked 
attacks  of  anger,  puerility,  weakness  of  memory,  and 
lack  of  concentration,  are  rarely  permanent,  although 
they  may  persist  for  a  considerable  period.  In  the 
chapter  on  Treatment  we  shall  discuss,  at  somewhat 
greater  length,  what  effect  serotherapy  has  had  upon 
the  frequency  of  the  occurrence  of  the  sequela?. 

Bibliography 

Altmann:    Klin.  Jahrbuch,  1906,  xv,  Heft  3,  627. 
Robb:    Brit.  Med.  Jour.,  1907,  ii,  1129. 

Brit.  Med.  Jour.,  1908,  i,  382. 
Ker:   Edinb.  Med.  Jour.,  1908,  i,  306. 
Sladen:     Jour.  Amer.  Med.  Assn.,  1908,  li,  1318. 
Ladd:     Jour.  Amer.  Med.  Assn.,  1908,  li,  1315. 
Koplik:    Med.  Record,  1908,  Ixxiv,  557. 
Mayerhofer:     Wien.  klin.  Wochenschr.,  1910,  xxiii,  651. 
Flexner:     Jour.  Exp.  Med.,  1913,  xvii,  553. 


CHAPTER  XVI 

Treatment 

History. — Although  the  life  history  of  the  disease 
is  but  little  over  a  century,  it  has  had  a  rich  and  varied 
therapeutic  career.  Chronologically  we  may  divide 
the  history  of  the  treatment  of  the  disease  into  seven 
chief  periods: 

1.  Drug  therapy. 

2.  Repeated  hot  baths. 

3.  Repeated  lumbar  punctures. 

4.  Permanent  drainage. 

5.  Intraspinal  injections  of  antiseptics. 

6.  Intraspinal  injections  of  diphtheria  antitoxin. 

7.  Specific  serotherapy. 

In  the  early  days  venesection,  which  was  then  the 
ordinary  mode  of  treatment  for  many  acute  diseases, 
was  also  employed  in  this  affection.  Then  came  the 
era  of  polypharmacy,  and  almost  every  drug  in  the 
pharmacopoeia  had  its  one-time  champion.  The 
vagaries  this  disease  exhibits  in  its  onset,  severity, 
course,  and  duration  readily  account  for  the  warm 
advocacy  of  one  drug  or  another  by  this  or  that 
observer.  It  is  but  natural  that  an  uncritical  observer, 
who  had  previously  passed  through  a  severe  epidemic, 
should  attribute  the  mildness  of  a  subsequent  one  to 

243 


244       MENINGOCOCCUS  MENINGITIS 

the  administration  of  a  new  drug.  But,  while  a 
comparatively  small  number  of  drugs  undoubtedly 
possess  some  power  in  relieving  a  number  of  the 
symptoms,  it  may  be  safely  stated  that  not  one  can 
lay  claim  to  specific  or  curative  action  upon  the 
disease. 

Similarly  we  must  deny  such  action  to  all  modes 
of  treatment  in  use  before  specific  serum  therapy 
entered  the  therapeutic  field.  Large  claims  have  been 
made  for  some  of  these  methods  and  each  one  had 
more  or  less  vogue  for  a  short  time.  A  larger  and 
more  varied  experience  showed  that  the  high  claims 
were  unfounded,  and  they  were  soon  discarded.  Thus 
it  was  with  the  injection  of  lysol  and  other  antisep- 
tics, and  thus  with  diphtheria  antitoxin.  Lumbar 
puncture  and  hot  baths  have  retained  their  places  in 
the  therapeutic  armamentarium,  but  merely  as  pallia- 
tive, not  curative  measures.  Surgical  procedures 
undertaken  for  the  purpose  of  relieving  high  intra- 
cranial pressure  or  securing  permanent  drainage  have 
thus  far  accomplished  little. 

Almost  hopelessly  the  medical  world  passed 
through  the  two  greatest  epidemics  in  the  history  of 
the  disease, — the  epidemic  in  New  York  in  1904- 
1905  and  the  one  in  Prussia  in  1905-1907.  Despite 
the  use  of  the  most  approved  methods  of  treatment, 
including  repeated  lumbar  punctures  and  hot  baths, 


TREATMENT  245 

the  rate  of  mortality  was  as  high  as  or  higher  than 
ever  before. 

Moreover,  theoretically  there  seemed  to  be  little 
likelihood  that  the  disease  would  ever  be  successfully 
combated  by  serotherapy.  Bacteriological  investiga- 
tions had  shown  that  the  meningococcus,  unlike  the 
diphtheria  bacillus  and  some  other  micro-organisms 
against  which  antitoxic  sera  had  been  successfully 
employed,  did  not  produce  its  pathogenic  effects 
through  the  agency  of  a  soluble  toxin  secreted  by  the 
living  organism.  But  most  of  the  previous  attempts 
at  the  production  of  effective  immune  sera  against 
other  infective  organisms  possessing  only  endotoxins 
(i.e.,  toxins  freed  only  after  the  disintegration  of  the 
bodies  of  the  organisms)  had  been  unsuccessful.  As 
in  these  cases  our  aim  is  not  so  much  to  neutralize 
toxin  as  to  destroy  the  infective  agent,  it  was  found 
that  by  merely  introducing  these  sera  into  the  general 
circulation  sufficiently  potent  effects  could  not  be 
produced.  Though  in  vitro  they  possessed  definite 
bacteriolytic  and  bacteriotropic  properties,  they 
failed  to  exert  such  action  in  the  body,  on  account  of 
our  inability  to  bring  about  sufficient  concentration 
of  the  immune  serum  within  the  immediate  vicinity  of 
the  organisms. 

Undismayed  by  these  unpromising  experimental 
considerations,  Kolle  and  Wassermann  and  Jochman 


246       MENINGOCOCCUS  MENINGITIS 

in  Germany,  and  Flexner  in  this  country,  undertook, 
practically  simultaneously,  a  series  of  researches 
aimed  at  the  production  of  a  serum  capable  of  de- 
veloping therapeutic  action  on  the  meningococcus. 
But  before  proceeding  to  state  the  important  results 
obtained  by  these  investigators,  the  fact  must  be 
mentioned  that  Bonhoff  and  Lepierre  had  previously 
produced  sera  which  seemed  to  possess  some  protective 
powers.  They  labored  under  the  distinct  disadvan- 
tage of  experimenting  with  small  laboratory  animals 
in  whom  it  could  not  be  positively  determined  whether 
death  was  due  to  infection  or  intoxication.  More- 
over, they  were  not  in  possession  of  a  method  suffi- 
ciently accurate  for  the  determination  of  the  biologic 
properties  of  their  immune  sera.  The  value  of  the 
sera  thus  not  being  definitely  proved,  their  work 
created  but  little  interest. 

The  previous  researches  of  Jaeger,  Kolle  and 
Wassermann  had  shown  that,  in  rabbits  and  horses 
immunized  with  cultures  of  the  meningococcus,  there 
developed  a  serum  possessing  well-marked  specific 
agglutinative  properties.  Loehlin  found  that  this 
serum  also  exerted  bacteriotropic  action.  Kolle  and 
Wassermann,  who  reported  their  results  in  the 
Deutsche  medimiische  Wochenschrift  of  April  19, 
1906,  after  injecting  horses  repeatedly  with  increas- 
ing doses  of  cultures  of  the  meningococcus  and  aque- 


TREATMENT  247 

ous  extract  of  the  organism,  succeeded  in  obtaining  a 
serum  which  exhibited  considerable  protective  powers. 
By  the  simultaneous  or  successive  injection  of 
aggressins  and  meningococci,  they  produced  a  fatal 
infection  in  guinea-pigs,  which  did  not  occur  previ- 
ously with  the  use  of  the  meningococcus  alone.  When 
the  immune  serum  was  employed  either  before  or 
after  the  injection  of  the  aggressins  and  meningo- 
cocci, the  animals  survived.  Moreover,  by  the  use  of 
the  complement  fixation  reaction,  they  demonstrated 
the  existence  of  specific  amboceptors.  Their  experi- 
mental results  led  them  to  advocate  the  subcutaneous 
injection  of  this  serum  as  a  therapeutic  agent  in  the 
human  infection. 

Jochmann's  paper,  which  was  published  in  the 
Deutsche  medizinische  Wochenschrift  of  May  17, 
1906,  describes  a  serum  which  he  proved  experi- 
mentally to  possess  bactericidal  and  bacteriotropic 
properties.  With  this  serum  were  treated  40  cases  of 
meningococcus  meningitis  at  the  Ratibor  Hospital. 
Seventeen  cases  were  treated  at  first  with  20  to  30 
cubic  centimetres  of  serum  injected  subcutaneously 
on  the  first  day  and  repeated  on  the  third  and  fourth 
days.  In  eleven  cases  the  injections  subsequent  to 
the  first  were  made  in  the  spinal  canal.  Five  of  the 
seventeen  cases  died,  three  of  the  deaths  being  in 
children  who  had  previously  developed  hydrocephalus. 


248       MENINGOCOCCUS  MENINGITIS 

In  nine  cases,  six  of  which  received  intraspinal  injec- 
tions, there  was  a  critical  fall  in  temperature  imme- 
diately following  the  treatment. 

Flexner,  whose  first  publication  on  the  subject 
appeared  in  the  Journal  of  the  American  Medical 
Association,  August  25,  1906,  began  his  studies  with 
an  investigation  of  the  biologic  properties  of  the 
meningococcus.  He  showed  that  the  rapid  disintegra- 
tion so  characteristic  of  this  organism  was  due  to  the 
action  of  an  intracellular  enzyme,  and  that,  as  a  re- 
sult of  the  destruction  of  the  cell  bodies,  there  was 
liberated  a  toxin  which  was  capable  of  producing 
inflammatory  changes  in  the  animal  body.  He  then 
succeeded  in  producing  in  certain  species  of  lower 
monkeys,  among  which  was  the  Macacus  rhesus,  an 
acute  leptomeningitis,  by  the  direct  injection  of  active 
cultures  of  the  meningococcus  into  the  subdural  space, 
which  presented  lesions  corresponding  to  those 
present  in  the  natural  disease  in  man.  When  he  pre- 
pared his  antiserum  he  was  enabled  to  test  its  value 
on  these  infected  monkeys. 

From  the  first,  Flexner  realized  that,  if  this  anti- 
serum is  to  exert  any  beneficial  action  upon  the  dis- 
ease, it  must  be  present  in  sufficient  concentration  in 
the  vicinity  of  the  organisms.  That  this  can  not  be 
accomplished  by  introducing  the  serum  subcutan- 
eously  becomes  evident  when  we  consider  the  enor- 


TREATMENT  249 

mous  dilution  the  serum  suffers  before  it  reaches  the 
infected  meninges.  Moreover,  it  had  previously  been 
shown  that  immune  bodies  pass  but  slowly  and  im- 
perfectly from  the  blood  into  the  cerebrospinal  fluid. 

Though  Jochmann  first  advised  the  intraspinal 
mode  of  injection  of  the  serum,  the  great  credit  for 
the  general  adoption  of  this  method  of  treatment 
clearly  belongs  to  Flexner.  He  not  only  insisted 
upon  its  importance,  but  offered  definite  and  con- 
vincing reasons  for  his  preferring  the  intraspinal 
route  for  the  administration  of  the  serum.  The 
failure  in  Germany  to  insist  on  this  point  and  the 
consequent  use  of  the  serum  subcutaneously  almost 
led  to  the  abandonment  of  the  serum  treatment,  as 
the  hopes  aroused  by  its  experimental  efficacy  were 
greatly  shattered  by  the  unsatisfactory  results  first 
obtained  in  the  human  disease. 

The  clinical  value  of  Flexner's  serum  was  soon 
shown  by  the  results  obtained  with  it  in  Akron, 
Castalia,  Philadelphia,  Baltimore,  Belfast,  and  Edin- 
burgh. In  Akron,  Ohio,  of  9  cases  of  meningitis 
not  treated  with  serum,  8,  or  89  per  cent.,  died;  where- 
as of  11  cases  treated  with  serum,  8,  or  72  per  cent., 
recovered.  Eliminating  two  fulminating  cases  from 
the  latter  series,  there  were  left  9  cases,  of  which 
8,  or  89  per  cent.,  recovered, — an  exact  reversal  of 
the  previous  results.   Similarly  favorable  results  were 


250       MENINGOCOCCUS  MENINGITIS 

observed  in  Castalia  and  Cleveland,  Ohio,  as  well  as 
in  Philadelphia,  Baltimore,  Belfast,  and  Edinburgh; 
so  that  Flexner  and  Jobling,  in  their  paper  in  the 
January  number  of  the  Journal  of  Experimental 
Medicine,  1908,  were  able  to  report  47  cases  of  menin- 
gococcus meningitis  treated  with  antiserum,  of  which 
34  recovered  and  13  died, — i.e.,  72.3  per  cent, 
recoveries. 

PREPARATION  OF  THE  ANTIMENINGITIS  SERUM 

There  are  at  present  in  use  a  considerable  number 
of  sera  which  differ  in  the  mode  of  their  preparation. 
The  sera  of  Flexner,  Kolle  and  Wassermann,  Dopter 
and  Jochmann  have  been  most  frequently  employed. 
In  this  country  that  of  Flexner  is  almost  exclusively 
used.  There  does  not  appear  to  exist  any  material 
differences  in  therapeutic  potency  between  the  sera 
above  mentioned.  Horses  are  employed  in  the  pre- 
paration of  all  of  them.  The  serum  of  this  animal 
is  less  injurious  to  the  human  body  and  is  obtainable 
in  sufficient  quantities. 

Flexner' s  Serum. — Cultures  of  a  large  number  of 
strains  of  the  meningococcus  killed  by  heat  at  60° 
C.  or  in  the  living  state  are  injected  alternately  with 
the  autolysate  of  the  organisms.  The  injections  are 
made  once  a  week  in  the  subcutaneous  tissues.  On 
account  of  the  severe  symptoms  which  occasionally 


TREATMENT  251 

followed  the  intravenous  injections,  this  mode  of 
immunization  had  been  discarded  by  Flexner.  The 
subcutaneous  injections  are  made  at  several  separate 
places  at  each  operation,  so  as  to  extend  the  area  of 
antibody  formation  and  reduce  the  intensity  of  the 
local  reaction.  The  injection  is  usually  followed  by 
a  rise  in  temperature,  and  local  swelling  which  dis- 
appears in  a  few  days.  Killed  cultures  are  used  dur- 
ing the  first  month  or  two. 

Kolle  and  Wassermann  Serum. — This  is  a 
mixture  of  three  different  sera: 

1.  Serum  derived  from  a  group  of  animals  which 
are  first  immunized  by  subcutaneous  and  intravenous 
injections  with  killed  and  later  with  live  cultures  of 
a  number  of  strains  of  the  meningococcus. 

2.  Serum  from  a  group  of  animals  repeatedly 
inoculated  with  a  highly  virulent  strain  of  the 
organism. 

3.  Serum  from  an  animal  that  has  been  repeatedly 
inoculated  intravenously  with  soluble  substances  de- 
rived from  different  strains  of  killed  meningococci. 

These  sera  are  mixed  and  heated  for  one  hour  at 
55°  C.  on  three  separate  days.  To  this  is  added  0.4 
per  cent  carbolic  acid  as  a  preservative. 

Jochmann  Scrum. — The  animals  are  inoculated 
with  killed  cultures  of  different  strains  of  the  menin- 
gococcus.   After  several  months,  live  cultures  are  in- 


252       MENINGOCOCCUS  MENINGITIS 

jected.  The  injections  are  at  first  made  in  the  sub- 
cutaneous tissues,  later  intravenously. 

Dopter. — The  animals  are  injected  intravenously 
with  increasing  doses  of  living  cultures  of  the  menin- 
gococcus.   Aqueous  extracts  are  not  employed. 

All  the  sera,  with  the  exception  of  that  of  Ruppel, 
are  polyvalent, — i.e.,  derived  by  the  use  of  many 
strains  of  the  meningococcus.  The  advisability  of 
this  mode  of  preparation  is  deduced  from  the  marked 
variations  in  virulence  and  agglutinogenic  power  ex- 
hibited by  different  strains  of  the  meningococcus. 
The  process  of  immunization  usually  requires  from 
five  to  six  months.  The  maximum  potency  of  the 
serum  is  usually  not  reached  before  one  year.  To  the 
German  and  American  sera,  carbolic  acid  is  usually 
added  as  a  preservative.  Dopter's  serum  is  submitted 
to  artificial  aging,  a  process  which  he  claims  tends  to 
reduce  the  frequency  of  serum  disease.  Kept  in  the 
refrigerator,  the  serum  usually  retains  its  potency 
for  a  long  time. 

MANNER  OF  THERAPEUTIC  ACTION 

Animal  experiments  and  test-tube  reactions  have 
shown  that  the  action  of  the  serum  is  attributable  to 
the  presence  of  a  number  of  immune  substances.  The 
most  important  of  these  are: 


TREATMENT  253 

1.  Bacteriolysins  or  antibacterial  substances. 

2.  Bacteriotropins   ( opsonins ) . 

3.  Anti-endotoxins. 

1.  Bacteriolysins. — The  serum  possesses  both 
direct  and  indirect  bactericidal  action.  It  directly 
inhibits  the  growth  of  the  meningococcus,  and  aids  in 
its  disintegration  without  the  intervention  of  leuco- 
cytes. Flexner  has  shown  that  weak  dilutions  have 
little  or  no  effect,  while  strong  concentrations  are 
highly  bactericidal. 

2.  Bacteriotropins. — The  experiments  of  Joch- 
mann,  Flexner,  and  Kolle  and  Wassermann  have 
demonstrated  that  the  serum  markedly  stimulates 
phagocytosis.  Flexner  has  shown  that  the  ingested 
meningococci  are  more  readily  disintegrated  than 
those  which  have  previously  not  been  subjected  to 
the  action  of  the  serum. 

3.  Anti-endotoxins. — The  serum  possesses  in  a 
moderate  degree  the  power  of  neutralizing  the  endo- 
toxin of  the  meningococcus.  The  autolysate  loses 
some  of  its  pathogenic  power  when  mixed  with  the 
antimeningitis  serum.  Its  possession  of  this  property 
is  by  most  of  the  investigators  attributed  to  the  in- 
jection of  autolysates  or  watery  extracts  of  the  menin- 
gococcus in  the  course  of  immunization.  Dopter, 
however,  claims  to  have  established  experimentally 
that  by  his  method  of  immunization,  in  which  only 


254       MENINGOCOCCUS  MENINGITIS 

living  meningococci  are  employed,  an  equal  if  not 
greater  quantity  of  anti-endotoxin  is  developed. 

Opinions  are  still  divided  as  to  whether  the  chief 
action  of  the  serum  is  due  to  its  bactericidal  or 
bacteriotropic  powers. 

In  addition  to  these  substances  the  serum  con- 
tains antibodies  which  bind  complement,  agglu- 
tinins, and  precipitins.  The  therapeutic  importance 
of  the  former  has  not  been  definitely  determined.  The 
content  of  agglutinins  is  no  measure  of  its  therapeutic 
activity.  On  the  presence  of  precipitins  depends  the 
value  of  the  precipito-reaction  of  Vincent  and  Bellot. 

STANDARDIZATION  OF  THE  SERUM 

The  serum  can  not  be  standardized  by  the  methods 
employed  with  the  antitoxic  sera.  Its  anti-endotoxic 
properties  can  not  be  used  for  titration,  as  its  strength 
is  probably  not  a  correct  measure  of  the  more  im- 
portant immune  principles  present  in  the  serum. 
Moreover,  the  meningococcus  autolysate  does  not 
possess  uniform  and  constant  pathogenic  action  on 
young  guinea-pigs  and  mice,  the  laboratory  animals 
which  are  most  susceptible  to  its  action.  The  serum 
can  not  be  tested  against  definite  quantities  of  living 
cultures,  on  account  of  the  great  fluctuations  in  their 
pathogenicity.  With  the  exception  of  Ruppel,  whose 
claims  have  thus  far  not  been  confirmed,  no  investiga- 


TREATMENT  255 

tor  has  succeeded  in  maintaining  the  pathogenic 
properties  of  the  living  cultures  at  a  fixed  and  suffi- 
ciently high  level. 

The  determination  of  the  strength  of  the  serum 
is  therefore  limited  to  test-tube  reactions.  None  of 
these  has  thus  far  proved  very  satisfactory.  The 
complement  binding  power  of  the  serum  has  been 
used  by  Kolle  and  Wassermann.  It  is  doubtful  if 
this  is  a  true  measure  of  its  therapeutic  activity.  Flex- 
ner  and  Jobling  standardize  the  serum  by  determin- 
ing its  opsonic  activity.  The  greatest  dilution  of  the 
serum  at  which  it  still  exercises  phagocytic  action 
exceeding  the  controls  is  taken  as  a  measure  of  the 
value  of  the  serum.  A  standard  serum  is  one  which 
when  diluted  five  thousand  times  still  shows  phago- 
cytic activity  above  the  control.  Flexner  states  that 
the  opsonins  or  bacteriotropins  of  the  serum  are 
highly  durable  and  persist  unchanged  when  kept  in 
the  refrigerator  for  one  year  or  longer. 

BASIC   PRINCIPLES  OF   SEROTHERAPY 

The  bacteriolytic,  bacteriotropic,  and  detoxicating 
action  of  the  serum  can  only  be  exerted  when  the 
immune  principles  on  which  these  effects  are  de- 
pendent are  brought  in  concentrated  form  in  the 
vicinity  of  the  meningococcus.  For  this  organism 
produces  its  pathogenic  effects  by  direct  and  local 


256       MENINGOCOCCUS  MENINGITIS 

action  on  the  tissues.    It  does  not  while  living  secrete 
a  soluble  toxin. 

That  accumulation  of  serum  in  the  cerebrospinal 
fluid  in  sufficient  concentration  can  not  take  place 
by  way  of  the  blood  is  due  to  two  causes:  first,  the 
high  dilution  it  suffers  in  the  blood  stream;  second, 
the  relatively   slight   permeability   of  the   meninges 
toward  complex  substances  present  in  the  circulation. 
This  fact  has  been  repeatedly  demonstrated.  Behring 
was  unable  to  find  diphtheria  antitoxin  in  the  cerebro- 
spinal fluid  after  its  introduction  in  the  subcutaneous 
tissue.     Similarly,   Quincke   failed  to  find  specific 
immune  principles  in  the  cerebrospinal  fluid.    Mac- 
kenzie and  Martin  have  shown  that  in  meningococcus 
meningitis   the   cerebrospinal  fluid   contains   neither 
complement  nor  bactericidal  amboceptors,  even  when 
they  are  abundantly  present  in  the  blood.     Agglu- 
tinins and  opsonins  were  present  only  in  traces.     It 
can  therefore  readily  be  seen  that  by  subcutaneous 
injections  of  the  serum  only  minimal  quantities  of 
the  immune  principles  will  reach  the  site  of  the  in- 
flammation in  the  meninges. 

But  while  the  passage  of  the  immune  bodies  from 
the  blood  into  the  cerebrospinal  fluid  is  very  slow  and 
imperfect,  the  absorption  of  these  substances  from  the 
cerebrospinal  fluid  into  the  blood  is  extremely  rapid. 
Debre,  by  employing  the  very  sensitive  precipitin  re- 


TREATMENT  257 

action  for  a  foreign  serum,  has  shown  the  rapidity 
with  which  absorption  takes  place.  The  reaction  ap- 
peared in  the  blood  about  ten  minutes  after  the  intra- 
spinal injection  of  foreign  serum.  In  meningitis  the 
serum  passed  into  the  general  circulation  even  more 
rapidly,  showing  that  the  inflamed  meninges  offer 
more  favorable  conditions  for  absorption. 

The  rapid  elimination  of  the  antimeningococcus 
serum  from  the  subarachnoid  space  has  been  shown 
by  Hohn  and  Dochez.  By  determining  the  protein 
contents  of  the  cerebrospinal  fluid,  Hohn  found  that 
the  serum  is  for  the  most  part  absorbed  within  twenty- 
four  hours.  Similarly  Dochez,  by  estimating  the 
antiproteolytic  ferment  in  the  serum,  showed  that  it 
tends  to  disappear  from  the  cerebrospinal  fluid  within 
twenty- four  hours. 

The  practical  deduction  to  be  drawn  from  these 
experimental  facts  is  obvious :  if  the  serum  is  to  exert 
its  maximum  effect  on  the  disease,  it  must  be  intro- 
duced directly  into  the  spinal  canal  at  frequent  inter- 
vals until  such  time  as  all  the  meningococci  are  de- 
stroyed. The  frequent  injections  are  necessary  to 
make  good  the  loss  in  concentration  of  the  serum  sus- 
tained by  its  rapid  absorption  into  the  blood.  We 
shall  see  that  these  are  the  principles  which  guide  us 
in  the  administration  of  the  serum. 

17 


258       MENINGOCOCCUS  MENINGITIS 

TECHNIC  OF  SERUM  ADMINISTRATION 

The  proper  procedure  for  performing  lumbar 
puncture  has  been  described  in  detail  in  a  previous 
chapter.  As  soon  as  the  pressure  in  the  subarachnoid 
space  has  reached  the  normal  level,  the  manometer  is 
detached  and  the  cylindrical  funnel  of  the  Quincke 
set  attached,  the  tubing  being  lowered  in  the  process 
so  as  to  keep  it  filled  with  cerebrospinal  fluid  (Fig. 
29).  The  funnel  is  then  filled  with  the  desired 
quantity  of  antimeningitis  serum,  which  had  previ- 
ously been  warmed  up  to  the  body  temperature  by 
placing  the  vial  containing  the  serum  in  hot  water. 
The  funnel  is  held  at  such  a  level  as  to  permit  the  slow 
passage  by  gravity  of  the  serum  into  the  subarachnoid 
cavity.  The  time  consumed  in  the  process  naturally 
varies  with  the  amount  of  serum  introduced,  but 
should  rarely  be  less  than  ten  minutes.  It  is  ex- 
tremely important  to  keep  the  needle  in  the  same 
position  throughout  the  whole  procedure,  and  thus 
prevent  displacement  of  the  point  of  the  needle  from 
the  spinal  canal.  The  injection  would  then  no  longer 
be  a  subarachnoid,  but  rather  an  epidural  or  sub- 
cutaneous one,  which,  as  we  have  seen,  is  practically 
valueless. 

The  serum  furnished  by  some  American  manu- 
facturers is  put  up  in  syringes,  which  are  attachable 


Fi<;    2'.t. — Aj>|  aratua  for  administrati  in  of  antin  emngitia  serum 


TREATMENT  2o9 

to  the  puncture  needle  by  a  short  piece  of  rather  too 
wide  tubing.  Personally  we  do  not  recommend  the 
use  of  a  syringe  for  the  introduction  of  the  serum  into 
the  spinal  canal.  The  injection  is  usually  too  rapid 
and  irregular,  and  undue  force  may  be  exerted,  caus- 
ing severe  compression  symptoms.  By  the  use  of 
gravity,  this  can  generally  be  avoided,  as  the  fluid 
runs  in  more  uniformly  and  slowly.  Moreover,  the 
rhythmic  changes  in  the  pressure  in  the  subarachnoid 
space  due  to  circulatory  and  respiratory  movements 
are  not  forcibly  overcome,  as  is  the  case  when  the 
serum  is  injected  by  syringe. 

The  condition  of  the  patient  must  be  very  closely 
watched  by  a  competent  assistant  and  the  operator 
immediately  informed  of  any  change  in  the  character 
of  the  respiration  and  pulse,  or  of  the  appearance  of 
cyanosis,  dilatation  of  the  pupils,  or  stupor. 

After  the  needle  is  withdrawn,  the  side  of  the 
puncture  is  covered  with  a  sterile  piece  of  gauze  and 
adhesive  plaster,  the  patient's  head  kept  low  and 
buttocks  raised  for  ten  minutes.  The  patient  is  then 
placed  in  bed,  the  foot  of  which  is  kept  raised  (8  to  12 
inches)  for  several  hours.  This  procedure,  first  ad- 
vised by  Jochmann  and  Schoene,  and  regularly  em- 
ployed by  Levy,  seems  to  aid  the  passage  of  the  serum 
into  the  cranial  cavity  and  its  diffusion  through  the 
whole  subarachnoid  space  and  ventricles.   The  patient 


260       MENINGOCOCCUS  MENINGITIS 

must  be  carefully  watched  for  at  least  fifteen  minutes 
by  a  physician  for  the  appearance  of  apnoea  or  other 
symptoms  of  collapse.  We  have  recently  adopted  the 
practice  of  performing  artificial  respiration  for  a 
short  time  on  all  cases  subsequent  to  the  injection  of 
serum.  In  this  manner  we  have  apparently  suc- 
ceeded in  preventing  the  occurrence  of  dangerous 
apnoea. 

Some  authors  advise  the  preliminary  injection  of 
morphine  in  order  to  avoid  the  great  restlessness  often 
exhibited  by  patients  during  this  treatment.  In 
children  at  least,  we  have  not  found  occasion  to  em- 
ploy this  drug.  General  anaesthesia  is  contraindicated, 
as  it  is  a  procedure  attached  with  considerable  danger. 
It  should  be  employed  only  when  the  unusual  vio- 
lence of  the  patient  would  otherwise  prevent  the  per- 
formance of  the  puncture. 

In  this  connection  we  must  speak  of  the  mode  of 
controlling  the  injection  of  the  serum  advised  by 
Sophian.  He  found  a  drop  in  blood-pressure  as  soon 
as  the  injection  of  serum  in  the  subarachnoid  space 
is  begun.  This  continues  steadily  as  more  and  more 
serum  is  introduced.  After  the  mercury  has 
dropped  20  to  30  millimetres,  the  continuance  of  the 
injection  leads  to  rapid  and  sudden  further  lowering 
of  the  blood-pressure.  He  cites  the  case  of  a  robust 
adult  in  whom  there  occurred  a  drop  of  30  milli- 


TREATMENT  261 

metres  of  mercury  after  the  i  ijection  of  only  12  cubic 
centimetres  of  serum.  On  injecting  3  cubic  centi- 
metres more  of  serum,  his  blood-pressure  dropped  30 
millimetres  more  at  one  bound,  making  a  total  drop 
of  60  millimetres  of  mercury.  The  clinical  signs  at 
the  time  did  not  indicate  shock,  the  pulse  continued 
to  be  fair  but  rapid,  the  color  good,  but  the  breathing 
was  shallow  and  somewhat  irregular.  A  few  minutes 
later  the  patient  suddenly  stopped  breathing,  which 
was  soon  followed  by  cessation  of  heart  action.  Death 
was  apparently  prevented  only  by  the  adoption  of 
active  measures. 

Sophian's  usual  technic  is  to  have  an  assistant  take 
blood-pressure  readings  throughout  the  whole  opera- 
tion. The  withdrawal  of  cerebrospinal  fluid  is 
stopped  when  the  arbitrary  drop  of  10  millimetres 
of  mercury  has  taken  place.  The  serum  is  then 
allowed  to  run  in  slowly  by  gravity,  the  funnel  being 
raised  or  lowered  to  regulate  the  rate  of  flow.  The 
injection  is  discontinued  when  in  an  adult,  whose 
average  blood-pressure  is  13  0  to  130  millimetres,  a 
total  drop  of  20  millimetres  of  mercury  has  taken 
place.  Hy  using  this  method  of  controlling  the 
amount  of  serum  injected,  he  has  found  that  the 
average  dose  of  serum  is  considerably  smaller  than 
that  usually  advised,  being  only  about  20  to  25  cubic 
centimetres  in  adults.    Despite  these  small  doses,  his 


262       MENINGOCOCCUS  MENINGITIS 

results  have  been  very  good.  His  observations  being 
based  on  about  200  cases,  the  method  would  seem  to 
deserve  further  trial.  We  have  had  no  personal 
experience  with  this  mode  of  controlling  the  ad- 
ministration of  the  serum.  It  would  seem  to  us  that 
in  infants  and  young  children,  the  marked  restless- 
ness so  often  present  during  the  operation  would 
seriously  interfere  with  the  accuracy  of  the  blood- 
pressure  readings. 

ROUTINE  METHOD  OF  TREATMENT  WITH  SERUM 

We  should  always  have  a  supply  of  serum  ready 
to  inject  when  performing  a  lumbar  puncture  on  an 
acute  case.  The  serum  should  be  injected  at  once, 
if  the  fluid  withdrawn  is  purulent  or  turbid,  without 
waiting  even  for  a  microscopic  examination.  If  the 
fluid  is  clear,  a  smear  preparation  should  be  made  and 
stained  by  the  Gram  stain.  If  meningococci  are  not 
demonstrable,  we  must  be  guided  by  the  clinical 
symptoms,  bearing  in  mind  that  clear  and  sterile 
fluid  is  not  infrequently  present  in  the  first  twenty- 
four  hours  of  the  disease.  While  the  injection  of 
serum  in  a  non-meningococcus  meningitis  will  do  no 
good  whatsoever,  it  at  least  will  do  no  harm.  On  the 
other  hand,  should  the  case  subsequently  prove  to  be 
one  of  meningococcus  meningitis,  the  injection  of 
serum  at  the  first  puncture  might  be  of  incalculable 


TREATMENT  263 

value  to  the  patient.  Our  duty  to  inject  serum  is 
clear,  if  there  is  the  least  doubt  lurking  in  our  mind 
as  to  the  nature  of  the  case.  Should  the  bacteriological 
examination  of  the  fluid  show  the  presence  of  organ- 
isms other  than  the  meningococcus,  no  further  injec- 
tions of  serum  are  given.  In  mixed  meningococcus 
infections  the  procedure  is  the  same  as  in  pure 
infections. 

All  observers  whose  opinions  are  based  upon  large 
experience  with  the  serum  treatment  are  now  in 
practical  accord  as  to  the  method  which  yields  the 
best  results.  In  malignant  cases  the  injection  should 
be  repeated  within  twelve  hours.  There  is  a  theoreti- 
cal objection  to  the  use  of  the  serum  in  these  cases  in 
the  possible  liberation  of  a  large  amount  of  endo- 
toxin, as  a  result  of  the  rapid  disintegration  of  the 
meningococci  brought  about  by  the  bacteriolytic 
action  of  the  serum.  But  such  consideration  should 
not  lead  us  to  withhold  the  possible  benefits  of  sero- 
therapy from  any  patient,  no  matter  how  desperate 
the  condition  is.  By  employing  it  in  apparently 
hopeless  patients,  the  case  for  the  serum  is  not  placed 
in  as  favorable  a  light  as  it  would  be  if  these  were 
excluded.  The  serum,  however,  is  no  longer  on  trial, 
and  the  literature  shows  that  occasionally  recovery 
has  taken  place  even  in  desperate  cases. 

In  cases  of  ordinary  severity,  we  should  inject 


264       MENINGOCOCCUS  MENINGITIS 

three  or  four  full  doses  at  twenty-four-hour  intervals. 
Even  should  marked  amelioration  of  the  clinical 
symptoms  appear,  it  is  not  advisable  to  discontinue 
the  injections  before  the  three  consecutive  daily 
treatments  have  been  given.  By  the  adoption  of  this 
systematic  mode  of  treatment,  we  can  best  guard 
against  the  occurrence  of  a  relapse. 

There  is  experimental  justification  for  the  repeti- 
tion of  the  injections  at  comparatively  short  intervals 
in  the  rapidity  with  which  the  cerebrospinal  fluid  rids 
itself  of  the  foreign  serum.  Unless,  therefore,  the 
supply  of  fresh  serum  is  kept  up  by  repeated  injec- 
tions, its  concentration  becomes  so  rapidly  reduced 
that  it  soon  fails  to  exert  in  full  its  beneficial  effects. 
In  very  mild  cases  one  dose  may  be  sufficient  to  de- 
stroy all  the  meningococci.  In  most  cases,  however, 
a  single  injection  is  inadequate  to  accomplish  this 
result.  Moreover,  it  is  of  the  utmost  importance  to 
achieve  this  result  in  one  continuous  course  of  treat- 
ment, otherwise  a  relapse  may  occur  after  a  long 
interval,  and  we  may  be  compelled  to  administer  the 
serum  in  the  anaphylactic  state  and  run  the  risk  of 
the  appearance  of  dangerous  symptoms. 

The  first  systematic  series  of  three  or  preferably 
four  consecutive  daily  injections  having  been  given, 
the  subsequent  course  of  treatment  to  be  pursued  will 


TREATMENT  265 

depend  upon  the  clinical  symptoms  present  and  the 
character  of  the  cerebrospinal  fluid.  Ordinarily  at 
this  time  the  temperature  will  be  normal,  the  mental 
condition  greatly  improved,  and  the  hyperesthesia 
and  rigidity  considerably  less  marked.  The  most 
trustworthy  indication,  however,  that  the  infection 
has  been  overcome  is  given  by  the  cerebrospinal  fluid. 
Usually  at  this  stage  it  is  clear,  the  adventitial  cells 
have  disappeared,  and  the  polynuclears  are  largely 
replaced  by  lymphocytes.  When  the  cerebrospinal 
fluid  has  assumed  this  character  and  the  meningo- 
cocci are  no  longer  demonstrable,  we  may  conclude 
that  the  infection  is  definitely  terminated  and  that 
no  further  serum  treatment  is  required. 

The  persistence  of  meningococci  in  the  fluid  de- 
mands the  continuance  of  daily  serum  injections  until 
such  time  as  they  shall  have  disappeared.  It  may  re- 
quire a  dozen  or  more  injections  to  bring  this  about, 
but,  unless  this  result  is  achieved,  there  is  no  certainty 
that  the  patient  has  escaped  the  danger  of  a  possibly 
fatal  relapse.  Such  an  eventuality  can  not  fairly  be 
charged  to  the  inefficacy  of  the  serum  when  it  is 
clearly  due  to  insufficient  treatment.  The  fear  of 
employing  too  large  a  (total)  quantity  of  serum  must 
not  deter  us  from  persisting  with  the  treatment  until 
a  definite  cure  is  achieved. 

Should,  at  any  period  of  the  disease,  symptoms 


266       MENINGOCOCCUS  MENINGITIS 

indicative  of  a  recrudescence  appear,  such  as  fever, 
headache,  hyperesthesia,  or  accentuation  of  the 
rigidity,  a  lumbar  puncture  must  at  once  be  per- 
formed. If  the  meningococcus  is  found  to  have  re- 
appeared, the  systematic  course  of  treatment  identical 
with  that  employed  during  the  primary  attack  must 
be  instituted. 

Even  in  the  absence  of  symptoms  presaging  a 
relapse,  it  is  advisable  to  repeat  the  punctures  at 
intervals  of  about  five  days  up  to  the  time  when  the 
cerebrospinal  fluid  has  assumed  its  normal  character 
(including  normal  pressure).  By  so  doing,  we  may 
occasionally  detect  the  earliest  beginning  of  a  re- 
lapse at  a  time  when  it  is  still  clinically  latent,  and 
thus  cut  short  its  course  by  judicious  treatment. 

Case. — H.  K.,  age  11  months,  admitted  January  1,  1913. 

Family  History. — Negative. 

Past  History. — Scalp  wound  five  months  ago  which  quickly 
healed.     Full-term  child;  breast  fed. 

Present  History. — Onset  four  days  ago  with  convulsions ; 
apathy  then  persisted  for  three  days,  except  for  slight  periods 
of  consciousness,  during  which  child  was  highly  irritable. 
Projectile  vomiting  during  first  three  days,  at  times  very 
frequent.    No  constipation. 

Examination, — Marked  Macewen,  marked  cervical  rigid- 
ity. Internal  strabismus,  bilateral  Babinski,  Oppenheim ;  no 
Kernig.    Slight  tenderness  along  spine. 


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Repetition  of  Lumbar  Puncture  after  an  Interval  of  Five  Days  to  ward  off  a 
Possible  Relapse. 


TREATMENT  267 

Leucocytes  34,000 ;  polynuclears  68  per  cent. ;  small 
lymphocytes  14  per  cent. ;  large  lymphocytes  16  per  cent. ; 
eosinophiles  2  per  cent. 

January  2 :  Lumbar  puncture :  25  cubic  centimetres  sub- 
arachnoid fluid  removed,  and  20  cubic  centimetres  of  Flexner's 
serum  injected.  Examination  of  fluid:  albumin  4  mm.;  re- 
duction 0;  cytology,  polynuclears  96  per  cent.,  mononu- 
clears 4  per  cent. ;  bacteriology,  contaminated.  Tempera- 
ture 104.4°  F. ;  pulse  158;  respiration  34. 

January  3 :  Lumbar  puncture :  20  cubic  centimetres  of 
subarachnoid  fluid  removed,  and  20  cubic  centimetres  of 
Flexner's  serum  injected.  Examination  of  fluid:  albumin 
8  mm.;  reduction  0;  cytology,  polynuclears  100  per  cent.; 
bacteriology,  few  Gram-negative  extracellular  bacilli ;  cultures 
negative.     Temperature  101°  F. ;  pulse  130;  respiration  34. 

January  7 :  Lumbar  puncture :  20  cubic  centimetres  of 
subarachnoid  fluid  removed ;  20  cubic  centimetres  of  Flexner's 
serum  injected.  Examination  of  fluid;  cytology,  no  cells  in 
sediment;  albumin  6  mm.;  reduction  0  (Fehling's)  ;  bacteri- 
ology, spreads  negative,  no  growth  in  media.  Temperature 
99°  F. ;  pulse  130;  respiration  30.  Marked  changed  for  the 
better  in  child's  general  condition. 

January  10:  Lumbar  puncture:  about  70  cubic  centi- 
metres of  cerebrospinal  fluid  withdrawn ;  first  specimen  blood 
tinged ;  second  clear.  Examination  of  fluid :  albumin  2  mm. ; 
reduction  present;  cytology,  bloody  sediment;  bacteriology, 
spreads  and  cultures  negative.  Temperature  99°  F. ;  pulse 
130;  respiration  34.  General  condition  good;  no  hydro- 
cephalus; no  rigidity  to  any  extent;  distinct  strabismus;  no 
Kernig;  slight  urticaria,  probably  due  to  scrum. 


268       MENINGOCOCCUS  MENINGITIS 

INTRAVENTRICULAR  INJECTION  OF  SERUM 

Though  in  the  large  majority  of  the  cases  the 
serum  reaches  in  sufficiently  concentrated  form  every 
part  of  the  nervous  system  that  is  bathed  by  cerebro- 
spinal fluid,  there  are  cases,  especially  in  infants, 
where  the  lack  of  any  favorable  influence  on  the 
course  of  the  disease  gives  us  reason  to  believe  that 
some  important  focus  of  infection  has  not  been 
reached  by  the  serum. 

In  most  of  these  cases  the  communication  between 
the  ventricles  and  the  spinal  subarachnoid  space  is 
shut  off  by  functional  or  organic  obliteration  of  the 
outlets  of  the  fourth  ventricle,  so  that  the  serum  in- 
jected in  the  lumbar  cul-de-sac  is  prevented  from 
reaching  the  infected  ventricles.  Aside  from  the 
evident  inemcacy  of  the  serum,  we  may  suspect  the 
existence  of  this  condition  if,  despite  demonstrable 
signs  of  hydrocephalus,  very  little  fluid  is  obtainable 
by  lumbar  puncture.  Moreover,  contrary  to  what  is 
the  case  when  the  communication  between  the  cranial 
and  spinal  cavities  is  free,  there  is  no  increase  in  the 
pressure  of  the  fluid  when  the  patient  is  changed  from 
the  recumbent  to  the  upright  position. 

In  these  cases  the  intraspinal  injection  of  serum, 
at  least  as  far  as  the  infection  of  the  ventricles  is  con- 
cerned, is   quite  as   devoid   of  value  as   is  its   sub- 


TREATMENT  269 

cutaneous  administration.  We  can  only  reach  the 
focus  of  infection  by  direct  intraventricular  injection 
of  the  serum.  In  these  cases  it  is  desirable  to  tap 
each  lateral  ventricle  on  alternate  days,  as  occasion- 
ally the  communication  between  them  is  obliterated. 

Tecknic  (Figs.  30  and  31). — This  is  not  attended 
with  unusual  difficulty  when  the  fontanelle  is  still 
open.  The  scalp  over  the  anterior  fontanelle  is 
shaved  and  rendered  surgically  aseptic  in  the  usual 
manner  or  by  the  use  of  tincture  of  iodine.  The 
needle,  which  is  about  8  centimetres  long,  is  inserted 
near  the  lateral  angle  of  the  fontanelle,  about  2.5 
centimetres  from  the  median  line,  and  is  gently 
pushed  downward  and  slightly  inward  toward  the 
median  line  to  a  depth  of  about  3  centimetres,  when 
the  cerebrospinal  fluid  will  usually  begin  to  flow. 
When  this  has  ceased,  a  quantity  of  serum  usually 
considerably  less  than  the  amount  of  fluid  withdrawn 
is  then  allovrd  to  flow  in  by  gravity.  In  older  chil- 
dren and  adults  a  trephine  hole  is  made  at  a  point  3 
centimetres  ibove  and  behind  the  external  auditory 
meatus  ( Kee  ne's  point )  before  tapping  the  ventricles. 

In  the  Children's  Service  of  Dr.  Koplik,  intra- 
ventricular injection  of  serum  was  performed  upon 
eight  cases.  In  some  the  lateral  ventricles  were  irri- 
gated with  a  weak  Gram  solution  previous  to  the  ad- 
ministration   of    the    serum.      All    the    cases    ended 


270       MENINGOCOCCUS  MENINGITIS 

fatally.  Intraventricular  administration  of  serum 
was  also  unsuccessful  in  the  hands  of  Cushing  and 
Netter.  Up  to  the  present  time  only  three  success- 
ful cases  are  reported  in  the  literature;  one  by 
Fischer,  another  by  Triboulet,  and  a  third  by  Levy. 

Posterior  Basic  Type. — L.  N.,  age  5^2  months ;  ad- 
mitted June  25,  1910;  died  August  1,  1910. 

Family  History. — Negative. 

Past  History. — Diarrhoea  for  last  two  weeks. 

Present  History. — Sudden  onset  four  days  ago  with  high 
fever.  Child  very  irritable.  Next  day  child  vomited  after 
each  feeding  (not  stated  whether  projectile  or  not),  and  same 
evening  had  a  convulsion.  Since  then  fever  has  persisted. 
Respirations  rapid.     Child  apathetic  unless  disturbed. 

Examination. — Child  sleeps  most  of  the  time;  irritable 
when  disturbed. 

Face :  Shows  weakness  of  left  side.  I  eft  orbital 
aperture  larger  than  right  and  eye  does  not  close  completely. 

Head :  Shows  marked  Macewen.  Fontanelle  bulging  and 
tense.     Neck  shows  slight  rigidity. 

Pupils  equal  and  regular.    No  ocular  palsi  s. 

Skin  shows  no  tache. 

Extremities :  Right  leg  moved  less  tha  i  left.  Slight 
rigidity  of  right  leg.     Slight  bilateral  Kernig. 

Clinical  Notes. — June  30:  Flatness  of  right  side  of 
face. 

July  2 :  Lumbar  puncture :  20  cubic  centimetres  with- 
drawn under  slight  pressure.  Fluid  cloudy ;  found  to  contain 
meningococci;   15  cubic  centimetres   of  Flexner's   serum  in- 


TREATMENT  271 

jected  at  once.  Child  comatose  during  procedure.  Artificial 
respiration  necessary. 

July  3:  Temperature  up  to  104°  F.  Child  very  irri- 
table. Head  retracted,  but  no  rigidity  of  neck.  Marked 
tache. 

July  4 :  Lumbar  puncture :  15  cubic  centimetres  of  cloudy 
fluid  withdrawn;  15  cubic  centimetres  of  Flexner's  serum 
introduced. 

July  5:  Anterior  fontanelle  tense.  Weakness  of  right 
face  the  same.  Circumference  of  head  44  centimetres.  Lum- 
bar puncture:  Introduction  of  30  cubic  centimetres  of  Flex- 
ner's serum.  General  condition  good.  Leucocytes  22,600 ; 
polymorphonuclears  77  per  cent. 

July  9:  General  condition  worse.  Anterior  fontanelle 
tense  and  pulsating.  Head  circumference  43*A  centimetres. 
Very  irritable,  marked  tache  and  Kernig.  Temperature 
ranged  from  104°  F.  to  normal. 

July  11 :  Brain  puncture  (lateral  ventricles)  and  lumbar 
puncture  by  Dr.  Elsberg.  Cloudy  fluid  from  both.  No 
organisms  found.  Serum  injected  into  spinal  canal  and 
ventricles. 

July  12:  Temperature  stayed  down  to-day.  General 
condition  somewhat  better. 

July   13:    Head  same  size,  431/.  centimetres. 

July  15:  For  past  three  days  temperature  has  gone  up 
to  103-104°  F.  in  evening.  General  condition  worse.  Kernig 
and  opisthotonus  marked. 

July  16:  Brain  puncture  (Dr.  Elsberg)  and  lumbar 
puncture  (Dr.  Heiman).  75  cubic  centimetres  of  turbid 
fluid  removed,  and  canal  irrigated  via  ventricles  with  saline 


272       MENINGOCOCCUS  MENINGITIS 

solution  colored  with  methylene  blue ;  30  cubic  centimetres 
of  Flexner's  serum  injected  into  canal.  Child  went  into  mild 
state  of  collapse,  but  recovered  after  a  few  hours. 

July  17 :  Signs  of  posterior  basic  pressure  less  marked. 
Still  considerable  neck  rigidity  and  Macewen.  Depression  of 
right  angle  of  mouth.  Slight  tache  and  Kernig.  Knee- 
jerks  have  reappeared.  Child  less  irritable;  takes  feedings 
well. 

July  18 :    Leucocytes  13,200 ;  polynuclears  64  per  cent. 

July  19 :    Circumference  of  head  43  centimetres. 

July  25 :  General  condition  slightly  better.  Head  in- 
creasing in  size.     Circumference  44  centimetres. 

July  28 :  Brain  puncture  by  Dr.  Elsberg:  Impossible  to 
get  fluid  from  lateral  ventricles  after  repeated  punctures. 
Finally  needle  inserted  into  third  ventricle,  and  orange- 
colored  turbid  fluid  withdrawn  under  high  pressure.  Lumbar 
puncture  by  Dr.  Heiman :  Few  drops  slightly  turbid  fluid 
obtained.  Irrigation  from  above  with  saline  methylene-blue 
solution.  After  fifteen  minutes  the  lumbar  fluid  began  to 
flow  faster,  but  it  was  not  colored  blue. 

July  30:  Lumbar  puncture:  70  cubic  centimetres  of 
clear  fluid  withdrawn  under  considerable  pressure;  30  cubic 
centimetres  of  serum  injected.     Child  reacting  well. 

August  1 :  General  condition  worse.  Pulse  weak  and 
rapid.     Twitching  of  extremities.     Ceased  to  breathe. 

USE    OF    SERUM    IN    COMPLICATIONS 

Recently  the  serum  has  also  been  employed  in  a 
number  of  complications  of  the  disease.    Ladd  after 


Fig.  30. — Intraventricular  puncture-  and  injection  of 

needle.      Netter  and  Debrfi 


Fig    ;i    -Direction  of  a lie  for  intraventricular  puncture  ;itm1  injection  of  serum, 

■  tei    iri.l  Deb 


TREATMENT  273 

aspirating  the  inflammatory  exudate  directly  in- 
jected the  serum  into  the  affected  joint.  This  was 
followed  by  rapid  improvement  in  the  condition.  In 
two  cases  of  meningococcasmia,  one  by  Bovaird  and 
the  other  by  Netter,  intravenous  injection  of  the 
serum  resulted  in  recovery.  The  serum  has  also  been 
successfully  employed  in  conjunctivitis  due  to  the 
meningococcus. 

DOSAGE 

The  dose  of  serum  is  measured  by  volume.  We 
have  no  definite  measure  of  the  efficiency  of  the 
serum,  as  is  the  case  with  diphtheria  and  tetanus  anti- 
toxins. It  is  rarely  advisable  to  introduce  a  larger 
volume  of  serum  than  cerebrospinal  fluid  withdrawn. 
In  cases  where  only  a  few  drops  of  thick  pus  are 
obtainable,  it  is  our  custom  to  inject  five  or  ten  cubic 
centimetres  of  serum.  At  the  next  puncture  we  have 
frequently  found  that  considerable  liquefaction  of  the 
purulent  exudate  has  taken  place  in  the  interval.  In 
infancy  we  usually  inject  ten  to  fifteen  cubic  centi- 
metres. In  adults  thirty  to  forty  cubic  centimetres 
are  usually  well  borne.  As  no  force  is  employed  in 
introducing  the  serum  by  the  gravity  method,  symp- 
toms of  compression  are  rarely  exhibited. 

The  total  quantity  of  serum  used  varies  greatly. 

18 


274       MENINGOCOCCUS  MENINGITIS 

In  protracted  cases  as  much  as  800  cubic  centimetres 
have  been  injected.  Netter  and  Debre  have  shown 
that  the  total  quantity  of  serum  injected  does  not 
play  an  important  role  in  the  frequency  or  severity  of 
the  serum  disease. 

RESULTS  OF  SERUM  TREATMENT 

When  the  nature  of  the  disease  is  borne  in  mind, 
it  need  not  greatly  surprise  us  that  the  early  clinical 
reports  on  the  action  of  the  serum  were  regarded  with 
considerable  scepticism.  Even  Flexner,  who  had 
proved  its  efficacy  in  experimental  meningitis,  ex- 
pressed himself  with  great  reserve.  A  disease  show- 
ing a  mortality  which  may  vary  from  30  to  80  per 
cent,  evidently  does  not  present  very  favorable  condi- 
tions for  the  exact  valuation  within  a  short  time  of 
any  therapeutic  agent. 

Moreover,  when  the  serum  was  first  employed, 
the  epidemic  outbreaks  both  in  America  and  Ger- 
many had  largely  subsided.  But,  as  has  been  re- 
peatedly stated,  at  such  a  period  the  disease  spon- 
taneously assumes  a  greatly  attenuated  character. 
So  it  was  but  natural  that  the  lower  death-rate  seen 
in  the  earlier  cases  treated  with  serum  should  have 
been  largely  attributed  to  the  decline  of  the  epidemic. 

With  wider  and  more  varied   experience,   how- 


TREATMENT  275 

ever,  it  soon  became  evident  that  at  last  we  were  in 
possession  of  a  potent  specific  agent  for  combating 
this  dread  disease.  The  first  convincing  proof  of  the 
efficacy  of  the  serum  came  when  it  was  for  the  first 
time  employed  at  the  height  of  a  very  severe  and  ex- 
tensive epidemic,  as  was  the  case  at  Belfast  and  Edin- 
burgh. When  it  was  employed  somewhat  later  in 
Paris,  its  efficacy  at  the  beginning  of  an  epidemic  — 
i.e.,  at  a  period  when  the  disease  usually  exhibits  its 
maximum  intensity — was  also  shown.  Its  potency 
was  again  in  evidence  in  the  recent  epidemics  in  the 
Southern  States.  At  the  present  time  the  curative 
value  of  the  serum  has  become  so  firmly  established 
that  we  need  hold  no  brief  for  its  use  in  meningo- 
coccus infections. 

The  large  body  of  observations  now  extant  in  the 
literature  shows  that  the  serum  is  efficacious  in  re- 
ducing the  mortality,  lessening  the  severity,  shorten- 
ing the  duration,  and  reducing  the  frequency  of  the 
complications  and  severity  of  the  disease. 

Effect  on  Mortality. — Practically  all  observers 
who  have  employed  the  serum  intradurally  in  suffi- 
cient dosage  attest  to  the  fact  that  a  notable  reduc- 
tion in  the  mortality  has  been  the  result.  The  follow- 
ing table,  which  is  based  upon  a  number  of  sources, 
shows  this  convincingly. 


276       MENINGOCOCCUS  MENINGITIS 


Reported  by- 


Flexner     (collect- 
ive)   

Netter 

Rob 

Ker 

Koplik 

Dunn 

Chase  and  Hunt. 

Sladen 

Fulton 

Ladd 

Levy 

Leick 

Neglein 

Kleinschmidt 
Quenstedt 


Serum  used. 


Dopter  (collective) . 
Schoene 


Jehle 

Weiss-Eder. 


} 


Flexner 
serum 


Kolle  and 

Wasserman 

serum 


Dopter 
serum 

Jochmann 
serum 

Paltant 
serum 


Cases  treated  with  serum. 


Number. 


{ 


1294 
100 
90 
30 
15 
40 
12 
23 
22 
31 

165 
34 

30 
21 
18 


402 
30 


41 
23 


Percentage 
mortality. 


30.9 

28 

30 

43 

13.3 

22.5 

25 

13 

31 

35.5 

18.18 
32.4 
26.6 
19 

22.2 


16.44 
25 


45 
39 


Percentage 

mortality  of 

cases 

treated  without 

serum. 


70-80 

49 

72.3 

80.5 

60 

70 

90 

64 

78.4 


52.14 

66 

50 

62.47 

56.2 


65 
53 


70 

85 


This  table  gives  the  gross  mortality  and  includes 
among  the  serum-treated  cases  a  number  of  deaths 
in  patients  moribund  when  the  treatment  was  insti- 
tuted. Moreover,  in  a  considerable  number  the  treat- 
ment was  not  sufficiently  vigorous  or  persistent.  In- 
cluded also  are  deaths  from  complications  which  had 
nothing  to  do  with  the  disease. 


TREATMENT 


277 


Despite  this,  a  comparison  with  the  cases  in  the 
same  vicinity  not  treated  with  serum  shows  that  the 
mortality  was  generally  reduced  to  one-half,  and  not 
uncommonly  to  one-third  or  one-fourth. 

In  this  connection  it  is  interesting  to  study  the 
distribution  of  the  fatalities  at  various  age  periods. 
There  are  available  for  this  purpose  the  tables  of 
Flexner,  Netter,  Dopter,  and  Levy,  which  are  given 
below. 


Less  than  1  year 

1-2  years 

2-5  years    

5-10  years 

10-20  years  

Above  20  yearB. 


Flexner. 


129 
87 
194 
218 
360 
288 


64 
27 
55 
33 
106 
108 


s  £ 

"-  B 


49.6 

31 

28.4 

15.1 

29.4 

37.50 


Netter. 


IS 
15 
22 
21 
11 
13 


15 
4 
6 
2 
2 
3 


ar 


61 

26.6 
27.2 
9.5 
18.1 
23 


Dopter. 


0)  o 


48.6 
20.1 
9.3 
8.5 
10.2 
14.1 


The  highest  mortality  was  seen  in  the  first  two 
years  of  life.  This  is  partly  attributable,  according 
to  Netter  and  Debre,  to  the  difficulties  encountered 
in  establishing  the  diagnosis  at  an  early  date.  More- 
over, at  this  age  there  is  a  tendency  to  the  rapid 
development  of  a  hydrocephalic  condition.    Yet  even 


278       MENINGOCOCCUS  MENINGITIS 

at  this  age  a  considerable  reduction  in  mortality  has 
been  effected.  The  rather  high  mortality  in  adults 
seen  in  Flexner's  collective  results  is  not  so  noticeable 
in  those  of  Netter  and  Dopter. 

Our  own  results  cover  49  cases  treated  with  Flex- 
ner's serum  at  the  Mount  Sinai  Hospital,  42  of  which 
were  admitted  to  the  Children's  Service  of  Dr. 
Koplik. 

The  mortality  at  the  various  age  periods  was  as 
follows : 


Cases  treated  with 
serum. 


No.  of 
cases. 


Deaths. 


Percent- 
age  of 
mortal- 
ity. 


Cases  not  treated  with 
serum. 


No.  of 
cases. 


Deaths 


Percent- 
age   of 
mortal- 
ity. 


Up  to  1  year .  . 

1-2  years 

2-5  years 

5-10  years .... 
Above  13  years 


14 
14 

8 
6 

7 


64.29 

57.14 

0 

0 

14.28 


10 

7 

10 

23 


7 

5 

4 

11 


70 
71.43 

40 
47.82 


We  thus  see  that,  while  up  to  two  years  of  age  the 
reduction  in  mortality  was  but  slight,  it  was  strik- 
ingly evident  in  the  ages  between  two  and  thirteen 
years.  There  was  not  a  single  fatality  in  the  fourteen 
cases  of  this  period,  whereas  the  mortality  at  this  age 
period  varied  between  40  and  47.82  in  the  33  cases 


TREATMENT 


279 


treated  between  1905  and  1908.  It  must  be  added 
that  the  diagnosis  was  established  by  the  demonstra- 
tion of  the  organism  in  the  cerebrospinal  fluid. 
The  importance  of  beginning  the  treatment  as 
early  as  possible  in  the  course  of  the  disease  is  strik- 
ingly shown  by  the  figures  of  Flexner,  Xetter, 
Dopter,  and  Levy. 


Levy. 

Netter. 

Flexner. 

Dopter. 

© 

oa 

S3 
O 

'o 
6 

OS 

© 

Q 

a  ■£ 
©  o 

sa 

o 

o 

d 
o 

0 

6 

© 

©  ^* 

5"a 
at, 
©  o 

© 

c3  ~Z 
Z   ~ 

ct 
©  o 
©  a 

•~  a 
© 

Ph 

-i 

at: 

©  o 

o   - 

-  = 
© 

1st  day | 

6 
33 

37 

24 
14 

11 
9 

26 

3 

7 

4 
3 
3 
3 

7 

9.09 
18.91 

16.66 
21.43 
27.27 
33.33 

26.92 

44 
32 
23 

9 

11 

6 

20.9 
33.3 
26 

18.1 
27.2 
36.5 

2d  day 1 

8  20 

3d  day 1 

4th  day i 

5th  day | 

14.40 

6th  day i 

7th  day J 

After  1st  week 

24.1 

The  figures  of  Levy  exhibit  the  remarkable  in- 
fluence the  date  of  the  first  injection  has  on  the 
prognosis  of  the  disease.  Of  39  cases  treated  in  the 
first  two  days  only  3  died,  and  these  within  thirty-two 
hours.  On  the  third  day  the  mortality  was  double 
that  of  the  second.  From  the  fourth  to  the  seventh 
day,  it  increased  about  6  per  cent,  each  day. 


280       MENINGOCOCCUS  MENINGITIS 


The  analysis  of  the  712  cases  at  the  various  age 
periods,  according  to  the  day  of  first  injection,  is 
given  in  a  very  instructive  table  by  Flexner. 


Percentage  mortality. 

Day  of  injection. 

1-2 

years. 

2-5 

years. 

5-10 

years. 

10-15 

years. 

10-20 
years. 

Over 
20. 

1st  to  3d  day 

7.7 
24.3 
49.1 

20.0 
25.8 
37.3 

10.9 
11.6 
20.8 

13.4 
31.1 
32.7 

13.4 
31.1 
32.7 

41.2 

4th  to  7th  day 

40.0 

Later  than  7th  day 

38.4 

It  appears  that  the  effect  of  the  time  of  the  first 
injection  is  of  most  importance  in  the  first  two  years 
of  life.  Injected  on  the  first  to  the  third  day,  the 
remarkably  low  percentage  mortality  of  5.6  was 
obtained.  The  mortality  rose  to  31.2  per  cent,  in  the 
cases  injected  from  the  fourth  to  the  seventh  day. 
At  a  period  later  than  this  60  per  cent,  of  the  cases 
died, — i.e.,  a  death-rate  approaching  that  seen  in  the 
ante-serum  days. 

The  supreme  importance  of  early  diagnosis  and 
treatment  in  this  group  of  cases,  which  usually  forms 
the  largest  contingent  of  an  epidemic,  can  not  well  be 
better  shown.  When  we  consider  that  at  this  tender 
age  the  delicate  structures  of  the  brain  offer  little 
resistance  to  the  inflammatory  process,  and  that 
hydrocephalus  readily  develops  as  a  result  of  the 
rapid  formation  of  adhesions  at  the  base  and  the 


TREATMENT  281 

yielding  character  of  the  cranial  coverings,  it  need  not 
surprise  us  that  the  slightest  delay  in  the  adoption  of 
specific  treatment  should  seriously  compromise  the 
chances  of  recovery. 

Effect  on  the  Symptoms. — The  serum  may  in- 
fluence all  or  only  a  part  of  the  symptoms,  according 
as  the  one  or  the  other  effect  takes  place.  Levy, 
whose  experience  with  serotherapy  has  thus  far  been 
the  most  extensive  of  any  single  observer,  divides  the 
cases  into  three  types. 

In  the  first  type,  which  forms  the  largest  con- 
tingent of  the  cases,  the  introduction  of  the  serum 
is  soon  followed  by  a  drop  in  temperature  to  the 
normal  either  by  lysis  or  crisis,  improvement  in  the 
general  condition,  diminution  of  the  hyperesthesia, 
heachache,  and  restlessness,  disappearance  of  de- 
lirium and  insomnia,  and  return  of  appetite  for  solid 
food.  The  characteristic  rigidity  of  the  neck  and 
Kernig  sign  may,  however,  persist  for  several  days 
or  a  week  after  all  the  other  symptoms  have  com- 
pletely disappeared. 

In  the  second  type  a  favorable  effect  is  shown  on 
all  the  symptoms  except  the  fever,  which  remains  at 
the  same  level  or  even  shows  a  tendency  to  rise  after 
each  injection.  After  a  few  days  the  temperature 
also  comes  down  to  normal,  and  recovery  is  complete. 

In  the  third  type  the  injections  are  not  followed 


282       MENINGOCOCCUS  MENINGITIS 

immediately  by  any  clinical  evidence  of  improvement. 
After  a  few  days  the  patient  begins  to  show  signs  of 
improvement,  which  is  very  gradual. 

According  to  Flexner,  there  is  a  critical  cessa- 
tion of  symptoms  in  about  30  per  cent,  of  the  patients 
that  recover.  With  the  amelioration  in  the  symptoms, 
there  is  usually  associated  a  diminution  in  the  degree 
of  polynuclear  leucocytosis  of  the  blood. 

Effect  on  the  Cerebrospinal  Fluid. — The  best 
index  of  the  effect  of  the  serum  on  the  disease  is  to  be 
found  in  the  cerebrospinal  fluid.  The  reason  for  this 
is  happily  expressed  by  Levy  thus:  "  In  no  disease 
are  we  presented  with  such  favorable  conditions  for 
the  study  of  the  action  of  a  therapeutic  agent  on  the 
causative  organism  and  the  local  inflammatory 
changes  produced  by  it,  as  in  meningococcus  menin- 
gitis. The  treatment  takes  place  under  ideal  experi- 
mental conditions.  It  may  truly  be  said  that  the 
cerebrospinal  canal  is  a  sealed  test-tube,  for  the  ex- 
periments of  Quincke  and  v.  Behring  show  that  not 
only  do  not  foreign  substances  pass  into  the  cerebro- 
spinal fluid,  but  also  such  complex  substances  as  the 
immune  bodies  which  are  formed  in  the  body  itself. 
The  canal,  therefore,  is  influenced  neither  from  with- 
in nor  from  without.  In  this  space,  filled  with  fluid 
containing  meningococci,  we  introduce  the  serum  and 


TREATMENT  283 

allow  it  to  act  at  body  temperature  on  the  organisms 
with  which  it  comes  in  direct  contact.  At  the  next 
puncture  we  have  the  opportunity  of  studying  under 
ideal  conditions  the  changes  that  have  taken  place  in 
the  interval.  Xo  test-tube  or  animal  experiment 
affords  better  opportunity  for  arrival  at  a  definite 
conclusion. 

Macroscopic. — The  consistency  and  cloudiness  of 
the  fluid  usually  diminish  with  each  successive  injec- 
tion. And  it  is  not  at  all  uncommon  for  the  fluid  to 
assume  its  normal  appearance  after  the  first  series  of 
consecutive  injections. 

Protein  Contents. — Despite  the  fact  that  the  fluid 
is  temporarily  enriched  by  the  introduction  of  the 
serum,  the  protein  percentage  diminishes  from  day 
to  day  in  favorable  cases.  The  quantitative  estima- 
tion of  the  proteins  during  the  course  of  the  treat- 
ment is,  therefore,  a  delicate  index  of  the  regression 
of  the  inflammatory  process. 

Cytologic  Changes. — The  effect  of  the  serum  is 
first  shown  in  the  disappearance  of  the  large  adventi- 
tial cells.  The  next  change  occurs  in  the  poly- 
morphonuclears, which  greatly  diminish  in  number 
and  become  less  degenerated.  With  the  diminution  in 
the  polymorphonuclears  there  occurs  simultaneously 
a  relative  increase  in  the  lymphocytes.     At  a  later 


284       MENINGOCOCCUS  MENINGITIS 

stage  these  cells  also  diminish  and  the  fluid  assumes 
its  normal  character.  The  replacement  of  the  poly- 
morphonuclears by  the  lymphocytes  occurs  also  in 
non-serum  cases  when  they  show  a  tendency  to  verge 
toward  chronicity.  In  the  serum  cases,  however, 
these  changes  occur  in  a  short  time,  and  indicate  the 
subsidence  of  the  inflammatory  process. 

Effect  on  the  Meningococci. — The  changes  in  the 
meningococci  demonstrable  after  the  injection  of  the 
serum  supply  the  last  link  in  the  chain  of  proof  de- 
manded by  those  who  remain  unconvinced  of  its 
efficacy  by  the  abundant  statistical  data.  In  most 
of  the  cases  their  number  is  greatly  diminished  and 
the  viability  on  artificial  culture-media  lost  after  the 
first  injection.  They  become  swollen  or  fragmented 
and  show  great  variability  in  staining.  As  a  rule, 
the  number  of  extracellular  organisms  diminishes 
first.  The  phagocytic  leucocytes  do  not  show  the  evi- 
dences of  degeneration  which  are  usually  seen  when 
serum  has  not  been  employed.  This  is  another  indi- 
cation that  the  ingested  meningococci  have  partly  lost 
their  vitality.  The  meningococci  usually  lose  entirely 
the  ability  to  take  the  stain  after  the  third  injection, 
so  that  they  are  no  longer  demonstrable  in  smear  pre- 
parations. Levy  gives  the  following  figures  as  to  the 
time  of  their  disappearance : 


TREATMENT  285 

In  18  cases  after  the  first  injection, 

In  33  cases  after  the  second  injection, 

In  35  cases  after  the  third  injection, 

In  14  cases  after  the  fourth  injection, 

In  9  cases  after  the  fifth  injection, 

In  4  cases  after  the  sixth  injection, 

In  1  case  after  the  eleventh  injection. 

Relapses. — All  observers  who  have  treated  the  dis- 
ease in  the  systematic  manner  described  above  have 
noted  the  paucity  of  relapses.  Indeed  Levy  has  seen 
so  few  relapses  that,  when  an  apparent  relapse  occurs 
after  ten  days  of  complete  absence  of  symptoms,  he 
looks  very  carefully  for  evidence  of  serum  disease. 
It  is  a  serious  therapeutic  error  to  inject  serum  in 
such  a  case  without  a  very  thorough  microscopic 
examination  of  the  cerebrospinal  fluid.  In  one  of  his 
cases  fatal  anaphylactic  shock  resulted. 

Effect  on  the  Duration  of  the  Disease. — We  have 
seen  that  the  duration  of  the  disease,  both  in  the  fatal 
and  recovered  cases,  is  very  variable.  In  123  fatal 
cases,  Xetter  found  that  the  disease  persisted  for 
more  than  one  month  in  77  and  for  more  than  two 
months  in  31.  In  83  recovered  cases  it  lasted  more 
than  one  month  in  37  and  more  than  two  months  in 
20.  The  average  duration  was  30  days.  In  350 
cases  of  the  recent  epidemic  in  New  York  (before 
the  introduction  of  the  serum),  Holt  found  that  the 


286       MENINGOCOCCUS  MENINGITIS 

disease  lasted  one  week  or  less  in  only  3  per  cent.,  and 
five  weeks  or  longer  in  50  per  cent. 

An  analysis  of  228  serum-treated  cases  by  Flex- 
ner  showed  that  the  duration  of  active  symptoms,  but 
not  including  the  time  required  for  the  disappearance 
of  the  rigidity  of  the  neck  and  the  Kernig  sign,  after 
the  first  injection  was  approximately  eleven  days. 

Levy  found  that  the  average  duration  in  127  of 
his  recovered  cases  was  12.5  days.  The  average 
duration  after  the  first  injection  was  only  6.86  days. 
He  considers  the  disease  terminated  when  the  fever 
and  symptoms  have  disappeared,  and  the  cerebro- 
spinal fluid  shows  no  marked  changes  from  the 
normal  character  and  no  longer  contains  meningo- 
cocci. 

Effect  on  the  Complications  and  Sequelae. — While 
these  have  varied  greatly  in  different  epidemics,  it  is 
usually  estimated  that  they  occur  approximately  in 
20  to  25  per  cent,  of  the  cases.  Netter,  before  the  use 
of  the  serum,  found  permanent  after-effects  of  the 
disease  in  23.5  per  cent.  In  the  Silesian  epidemic 
they  occurred  in  25  per  cent. 

Since  the  adoption  of  serum  treatment,  Netter 
has  observed  such  sequelae  in  only  6.3  per  cent., 
Dopter  in  6.2  per  cent.  In  295  recovered  cases  Flex- 
ner  reports  only  3.4  per  cent.  This  observer,  in  his 
most  recent  publication,  gives  a  table  on  the  occur- 


TREATMENT 


287 


rence  of  impaired  hearing  and  vision  and  arthritis  in 
serum-treated  eases,  which  we  here  reproduce. 


Day  of  disease  of  first  serum  injection. 

d 

>. 

CJ 

•a 

>> 

CJ 

-a 
co 

>> 

CJ 

■a 

.a 
5 

>> 

cj 
13 
A 

>> 

a 

-a 

>> 

d 

-a 

o 
o 

& 

J3 

z* 

co 

"3 

0 

Number  of  cases  in 
which      deafness 
occurred 

Number  of  cases  in 
which     impaired 
vision  occurred. . 

Number  of  cases  in 
which      arthritis 
occurred  

1 

1 

15 
5 

6 
3 

5 
2 

1 

3 
2 

3 

1 

7 
3 
2 

4 

4 

45 
12 
11 

Deafness  was  complete  in  39,  and  partial  in  6. 

Blindness  occurred  3  times. 

Impaired  mentality  was  seen  3  times. 

Paralysis  occurred  in  11  cases  as  follows: 
Strabismus  in  5 ;  lower  extremity  3 ;  of  the  face  in  2 ; 
and  of  the  shoulder  in  1.  It  can  be  seen  that  of  all 
the  severe  sequelae,  hearing  remains  the  least  in- 
fluenced (3.5  per  cent.). 

Levy,  who  observed  after-effects  in  15.5  per  cent., 
attributes  his  higher  figures  to  the  fact  that  many  of 
the  complications  were  already  developed  at  the  time 
the  patients  were  admitted  to  the  hospital.  The  most 
common  after-effects  were  deafness  and  blindness. 
All  forms  of  paralysis  present  in  the  height  of  the 
disease  resulted  in  complete  functional  restoration. 


288       MENINGOCOCCUS  MENINGITIS 

Levy  did  not  observe  any  cases  in  which  idiocy,  im- 
becility, or  even  milder  psychical  changes  appeared 
after  the  patients  left  the  hospital. 

Serum  Disease. — This  condition,  which  was  first 
described  under  this  name  by  v.  Pirquet  and  Schick, 
is  one  commonly  seen  after  the  subcutaneous  injec- 
tion of  diphtheria  antitoxin.  It  is  due  to  the  intro- 
duction of  foreign  serum  in  the  circulation.  It  seems 
that,  when  foreign  serum  is  injected  by  the  intra- 
dural route,  serum  disease  occurs  even  more  fre- 
quently than  when  introduced  subcutaneously.  In 
serum-treated  cases  this  condition  develops  in  about 
one-third  or  one-half  of  the  cases,  whereas  in  diph- 
theria it  occurs  in  only  about  15  per  cent,  of  the  cases. 
The  symptoms  usually  appear  from  eight  to  ten  days 
after  the  first  injection  in  the  form  of  fever,  urticarial 
or  erythematous  eruption,  arthralgia,  regional  en- 
largement of  the  lymph-nodes,  digestive  disturbances, 
and  albuminuria.  These  symptoms  occur  somewhat 
less  frequently  in  the  infant  than  in  the  older  child  or 
adult.  Netter  and  Debre  have  shown  that  the  total 
amount  of  serum  injected  does  not  greatly  influence 
the  frequency,  time  of  appearance,  or  severity  of  the 
serum  disease. 

When,  however,  the  injection  is  given  in  the  ana- 
phylactic state  (i.e.,  a  week  or  more  after  a  previous 
subcutaneous   or   intradural   injection   of  a   foreign 


TREATMENT  289 

serum),  much  more  severe  symptoms  may  appear 
within  a  few  hours.  The  eruption,  which  is  more 
marked,  may  be  accompanied  by  high  fever,  chill, 
prostration,  and  intense  dyspnoea  due  to  oedema  of 
the  glottis  and  trachea  or  pulmonary  oedema.  Usually 
they  subside  in  a  short  time  and  do  not  lead  to  serious 
results. 

In  a  small  number  of  cases,  which  have  been  well 
described  by  Xetter  and  Debre,  the  serum  disease 
may  manifest  itself  in  the  form  of  meningeal  oedema, 
analogous  to  the  laryngeal  oedema  occasionally  seen 
in  the  convalescence  from  laryngeal  diphtheria.  The 
selective  localization  in  these  cases  is  probably  due  to 
lack  of  resistance  on  the  part  of  the  previously  in- 
flamed tissues. 

There  is  a  sudden  rise  of  temperature,  general 
malaise,  restlessness,  and  insomnia.  The  rigidity  of 
the  neck  and  Kernig  sign,  which  may  have  disap- 
peared or  become  attenuated,  appear  once  more  or 
become  greatly  accentuated.  Relapse  is  suspected, 
especially  as  an  urticarial  eruption  is  frequently 
absent.  Recognition  of  the  true  nature  of  the  condi- 
tion is  extremely  important,  as  failure  to  do  so  may 
lead  to  the  adoption  of  a  mode  of  treatment  which 
seriously  jeopardizes  the  patient's  life.  A  correct 
diagnosis  is  made  by  lumbar  puncture,  which  shows 


290       MENINGOCOCCUS  MENINGITIS 

clear  fluid  containing  few  cells  and  no  meningococci. 
The  condition  clears  up  within  a  short  time. 

Should,  however,  serum  be  injected  under  the 
mistaken  idea  that  a  relapse  is  threatened,  the  symp- 
toms will  become  greatly  aggravated  within  a  few 
hours,  as  we  would  then  be  treating  serum  disease 
with  serum.  In  one  such  case  Levy  saw  a  fatal  re- 
sult occur. 

Untoward  Results  from  Serum  Administration. 
— Restlessness,  vertigo,  vomiting,  painful  sensations 
in  the  lumbar  region  and  lower  extremities,  vesical 
and  rectal  tenesmus  are  occasionally  seen  during  or 
immediately  after  the  administration  of  the  serum. 
The  local  symptoms  are  probably  due  to  stretching  of 
the  lower  nerve-roots  by  the  injected  serum.  In  a 
certain  number  of  cases  there  appears,  during  the 
operation  or  immediately  after,  a  train  of  symptoms 
indicating  shock.  Several  factors  may  be  concerned 
in  its  causation, — too  great  or  too  sudden  change  in 
cerebrospinal  pressure,  rapid  liberation  of  endo- 
toxins, or  hypersensibility  to  the  foreign  serum.  The 
earliest  and  most  important  symptom  indicating  the 
approach  of  shock  is  a  change  in  the  character  of  the 
respiration.  The  breathing  becomes  slow,  shallow, 
and  irregular.  Occasionally  it  is  deep  and  stertorous. 
With  this  there  are  often  associated  pallor  or  cyanosis, 
dilation  of  the  pupils,  general  relaxation,  convulsive 


TREATMENT  291 

movements  of  the  face  and  limbs,  and  stupor.  The 
pulse,  while  usually  feeble  and  irregular,  is  occa- 
sionally very  deceptive,  as  it  will  continue  to  be  fair 
when  the  respirations  have  become  markedly  altered 
in  character. 

Upon  the  earliest  appearance  of  these  symptoms, 
no  time  must  be  lost.  The  one  measure  which  has 
succeeded  best  in  our  hands  has  been  vigorous  arti- 
ficial respiration  continued  for  ten  minutes  to  one- 
half  hour.  While  this  is  being  continued,  an  assistant 
should  do  cardiac  massage  and  inject  hypodermically 
camphor  in  ether,  adrenalin  and  atropine.  In  a 
number  of  cases  the  prompt  adoption  of  these 
measures,  particularly  artificial  respiration,  has  been 
directly  instrumental  in  saving  life.  As  long  as  there 
is  evidence  of  cardiac  action,  the  attempts  at  revival 
of  the  patient  should  not  be  abandoned. 

The  injection  may  be  followed  by  weak  and  irreg- 
ular pulse,  restlessness,  headache,  twitchings,  and 
pain  in  the  back  and  lower  extremities.  These  symp- 
toms usually  subside. 

Levy  has  observed  quite  frequently  a  consider- 
able rise  in  temperature  and  temporary  aggravation 
of  the  meningitic  symptoms,  which  he  attributes  to 
the  rapid  liberation  of  the  endotoxin  resulting  from 
the  bacteriolytic  action  of  the  serum.  His  opinion 
is  based  upon  the  fact  that  the  temperature  did  not 


292       MENINGOCOCCUS  MENINGITIS 

rise  when  meningococci  were  no  longer  present  in  the 
fluid. 

Causes  of  Failure  "with  Serum  Treatment. — Lack 
of  success  with  the  specific  treatment  may  be  due  to 
several  causes.  When  the  vital  centres  in  the  brain 
are  seriously  compromised  before  the  treatment  is 
begun,  little  effect  from  the  serum  can  be  expected. 
In  the  fulminating  cases  the  intense  and  rapid  endo- 
toxication  can  not  well  be  combated  by  a  serum  whose 
detoxicating  powers  are  comparatively  feeble.  In  a 
certain  number  of  cases  complications  having  no 
direct  connection  with  the  disease,  such  as  tubercu- 
losis, bring  about  a  fatal  result,  despite  the  beneficial 
action  of  the  serum  upon  the  meningococcus  infec- 
tion. In  infants  failure  is  often  due  to  the  early 
development  of  hydrocephalus.  Last,  but  not  least, 
of  the  factors  which  lead  to  failure  is  incomplete, 
insufficient,  or  unskilled  use  of  the  serum.  The  more 
favorable  results  obtained  by  those  who  are  fully  con- 
versant with  this  method  of  treatment  show  the  im- 
portance of  this  factor. 

It  must,  however,  be  admitted  that  in  a  certain 
number  of  cases  the  infecting  organism  seems  to  be 
refractory  to  the  action  of  the  serum.  This  is  prob- 
ably due  to  the  existence  of  strains  of  meningococci 
which  are  fast  to  the  serum  employed.  It  has  not  yet 
been   definitely   determined  whether  this   is   due  to 


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TREATMENT  293 

resistance  to  solution  by  the  intraleucocytic  enzymes 
or  to  resistance  to  immune  opsonins  or  bacterio- 
tropins.  It  may  be  hoped  that,  by  the  employment 
of  a  number  of  these  resistant  strains  for  the  produc- 
tion of  specific  antiserum,  the  cases  refractory  to  the 
therapeutic  action  of  the  serum  will  become  less  and 
less  numerous. 

As  an  illustration  of  the  so-called  fast  cases  of 
meningococcus  meningitis,  the  following  two  cases 
which  recently  came  under  observation  showed  how 
refractory  these  fast  cases  are  to  the  antimeningitis 
serum  at  present  supplied  for  treatment.  The  salient 
features  of  these  cases  were,  that  they  both  came  from 
the  same  neighborhood,  becoming  infected  about  the 
same  period  of  time,  and  that  numerous  injections  of 
antimeningitis  serum  were  given  with  no  apparent 
effect.  We  would  suggest,  in  view  of  the  above  facts, 
that  strains  of  these  meningococci  should  be  properly 
cultured  and  inoculated  for  the  purpose  of  establish- 
ing a  fast  serum  for  this  class  of  cases.  The  ac- 
companying temperature  charts,  on  which  the  time 
of  injections  is  indicated,  will  show  how  ineffectual 
the  antimeningitis  serum  which  has  not  been  prepared 
from  fast  strains  is  in  these  cases. 

As  has  been  previously  stated,  Dopter  finds  that 
in  some  cases  of  meningitis  the  infecting  organism  is 
not  the  meningococcus  but  the  closely  allied  para- 


294       MENINGOCOCCUS  MENINGITIS 

meningococcus.  For  these  cases  he  advises  the  use  of 
the  antiparameningococcus  serum  prepared  by  him. 
Favorable  results  are  reported  by  a  number  of  French 
observers. 

SYMPTOMATIC    TREATMENT,    ETC. 

With  the  introduction  of  specific  serotherapy,  the 
symptomatic  treatment  of  the  disease  has  assumed 
secondary  importance.  There  are  a  number  of 
symptoms  which  at  times  must  be  temporarily  com- 
bated with  drugs  or  other  measures  until  the  serum 
shall  have  exerted  its  curative  action.  The  most  im- 
portant of  these  are  restlessness,  headache,  vomiting, 
insomnia,  and  convulsions.  The  restlessness  is  quite 
frequently  greatly  relieved  by  the  use  of  bromides 
(gr.  iii  to  x,  according  to  age).  Occasionally  it  is 
advisable  to  combine  chloral  hydrate  (gr.  ii  to  viii) 
with  the  bromides.  This  combination  is  also  useful  in 
diminishing  the  tendency  to  convulsions.  The  head- 
ache is  best  treated  by  an  ice  helmet  applied  inter- 
mittently to  the  head.  The  insomnia,  which  is  a  pro- 
nounced symptom  in  many  cases,  is  often  relieved  by 
veronal  (gr.  ii  to  x)  or  trional  (gr.  ii  to  x),  either 
alone  or  in  combination. 

It  is  customary  to  administer  sodium  or  potassium 
iodide  (gr.  iii  to  x)  empirically.  It  is  claimed  that  it 
limits  the  inflammatory  process  and  in  the  later  stages 


TREATMENT  295 

aids  the  absorption  of  the  exudate.    It  is  very  doubt- 
ful whether  such  action  is  ever  exerted  by  this  drug. 

Recently  the  use  of  urotropin  has  been  advocated 
in  this  disease,  as  it  has  been  shown  by  Crone  that, 
subsequent  to  its  administration  by  mouth,  formalde- 
hyde appears  in  the  cerebrospinal  fluid.  We  are  not 
in  possession  of  sufficient  clinical  data  for  the  estima- 
tion at  the  present  time  of  the  value  of  this  mode  of 
treatment.  At  any  rate,  it  is  advisable  to  administer 
it  in  moderate  doses  (gr.  ii  to  vii),  combined  with 
large  quantities  of  water,  to  the  patient  as  well  as  to 
all  members  of  the  patient's  family,  as  a  possible 
prophylactic  measure. 

Lumbar  Puncture. — On  theoretical  grounds,  we 
might  expect  that  the  withdrawal  of  fluid  from  the 
spinal  canal  would  exert  a  definitely  favorable  effect 
on  the  disease.  The  removal  of  a  certain  amount  of 
exudate  and  a  more  or  less  large  number  of  organisms 
should  diminish  the  inflammatory  process  in  the 
meninges.  Clinical  observation  and  statistical  data, 
however,  have  shown  that  lumbar  puncture  rarely 
exerts  any  but  temporary  effect  on  the  course  of  the 
disease.  It  may  temporarily  relieve  headache,  rest- 
lessness, hyperesthesia,  and  convulsive  phenomena. 
Rut  within  twelve  to  twenty-four  Ik  tins  there  is 
usually    a    return     of    symptoms     present     before 


296       MENINGOCOCCUS  MENINGITIS 

puncture.  In  extremely  rare  cases  convalescence  has 
set  in  after  one  lumbar  puncture. 

In  the  recent  Silesian  epidemic,  Goeppert  has 
shown  that  the  mortality  rate  was  not  lowered  by  the 
use  of  lumbar  puncture. 

In  acute  hydrocephalus  occurring  at  the  onset  of 
the  disease,  lumbar  puncture  is,  without  doubt,  at 
times  a  life-saving  procedure.  In  this  condition  is 
found  the  chief  indication  for  the  employment  of  this 
measure  in  the  therapy  of  this  disease. 

In  subacute  and  chronic  cases  it  is  indicated  on 
the  appearance  of  symptoms  of  increased  intra- 
cranial pressure,  such  as  Macewen  sign,  rise  of 
temperature,  headache,  vomiting,  convulsions,  and  in- 
crease of  hyperesthesia  and  rigidity.  If  no  meningo- 
cocci are  present  in  the  fluid,  the  serum  should  not  be 
injected.  Needless  to  add,  spinal  puncture  is  use- 
less if  there  is  occlusion  of  the  outlets  of  the  fourth 
ventricle. 

Passive  Hypercemia  (Bier). — This  procedure  has 
been  recommended  by  Vorschuetz.  He  advises  the 
application  of  the  bandage  for  twenty-two  hours 
after  a  preliminary  lumbar  puncture.  He  claims 
marked  relief  from  this  mode  of  treatment.  Its  field 
of  usefulness  remains  to  be  determined. 

Hot  Baths. — This  method  of  treatment  was  intro- 


TREATMENT  297 

duced  by  Aufrecht  in  1894,  and  has  since  been  ex- 
tensively employed.  In  many  cases  the  use  of  the  hot 
baths  is  followed  by  relief  of  pain,  hypersesthesia, 
delirium,  and  insomnia,  and  occasionally  by  a  drop  in 
temperature.  Other  patients  experience  no  relief, 
and  are  indeed  made  worse  by  the  manipulations.  In 
cases  where  favorable  action  is  exerted  by  the  baths, 
they  may  be  repeated  three  times  a  day.  The 
temperature  of  the  bath  should  be  about  104°  F.  and 
its  duration  from  ten  to  twenty  minutes.  At  best  the 
use  of  the  hot  baths  is  merely  a  palliative  measure. 
They  do  not  influence  the  course  or  duration  of  the 
disease. 

Treatment  of  Com  plications. — The  arthropathy 
is  usually  of  such  a  mild  nature  that  immobilization  is 
ordinarily  sufficient.  For  pain  it  is  well  to  try  moder- 
ate doses  of  aspirin  and  the  local  use  of  methyl 
salicylate.  In  suppurative  arthritis,  as  we  have  seen, 
the  serum  has  been  successfully  injected  in  the  joint. 
The  treatment  of  other  complications,  such  as  pneu- 
monia, pleurisy,  endocarditis,  and  paralysis,  is 
carried  out  along  the  usual  lines. 

Treatment  of  Serum  Disease. — It  is  well  to  ad- 
minister a  laxative  in  the  form  of  castor  oil  or  calo- 
mel. Alleviation  of  pruritus  is  usually  accomplished 
by  warm  bicarbonate  of  soda  baths  and  the  local  use 


298       MENINGOCOCCUS  MENINGITIS 

of  1  per  cent,  menthol  lotion.  In  severe  cases  anti- 
pyrine  may  be  administered. 

Use  of  Vaccines. — As  in  the  chronic  cases  the  use 
of  serum  is  not  as  efficacious  as  in  the  acute,  it  might 
be  well  to  try  the  use  of  vaccines.  Favorable  results 
are  to  be  expected  only  from  the  autogenous  vaccines. 
These  may  be  given  in  doses  of  100  to  500  millions 
at  intervals  of  four  to  five  days. 

Surgical  Procedures. — A  number  of  surgical 
operations  have  been  jDroposed  for  the  relief  of  intra- 
cranial pressure.  In  some  of  these  the  attempt  has 
been  made  to  secure  permanent  drainage.  The  most 
important  of  these  procedures  have  been  laminec- 
tomy, incision  of  the  occipital  ligament,  craniotomy 
with  through  and  through  drainage.  Haynes  has 
devised  an  operation  for  draining  the  cisterna  magna, 
for  which  he  claims  a  minimum  of  risk,  simplicity  of 
technic,  and  ease  of  execution.  Although  his  three 
cases,  which  were  in  a  hopeless  condition  before 
operation,  died,  they  were  distinctly  relieved  for  a 
short  time  by  the  procedure.  We  may  say  of  all  the 
surgical  procedures  thus  far  proposed,  that,  while 
temporary  relief  has  occasionally  followed,  it  re- 
mains to  be  proved  that  they  are  capable  of  exert- 
ing a  durable  effect  on  the  disease. 


TREATMENT  299 

GENERAL  MANAGEMENT 

Next  in  importance  to  the  treatment  with  serum 
is  that  of  the  general  care  of  the  patient.  The  patient 
is  kept  in  bed  for  at  least  a  week  after  the  temperature 
has  become  normal  and  the  active  symptoms  have 
subsided.  The  proper  nutrition  of  the  invalid  must 
be  maintained.  Generally  the  appetite  is  fairly  well 
preserved  and  no  great  difficulty  is  encountered  in 
persuading  patients  to  take  sufficient  quantities  of 
food.  Occasionally,  however,  when  the  patient  is 
comatose,  nourishment  by  mouth  is  refused,  and  the 
problem  of  adequate  nutrition  becomes  paramount. 
While  rectal  alimentation  with  peptonized  milk, 
broth,  and  eggs  is  useful  for  a  short  period,  it  is 
rarely  tolerated  for  any  length  of  time.  In  this 
eventuality  it  becomes  necessary  to  feed  the  patient 
by  means  of  gavage  or  nasal  feeding.  At  times  this 
form  of  alimentation  has  to  be  maintained  for  a 
period  of  weeks.  In  breast-fed  babies  it  is  desirable 
to  continue  the  breast  feeding.  Goeppert  has  shown 
that  the  prognosis  is  noticeably  better  in  the  breast- 
fed than  in  the  bottle-fed  babies. 

During  the  height  of  the  disease  the  diet  should 
consist  of  milk,  broths,  and  gruels.  Soft  diet  should 
be  resumed  on  the  subsidence  of  febrile  temperature. 
It  is  not  desirable  to  restrict  the  diet  unnecessarily, 
as  the  digestive  functions  are  frequently  not  greatly 


300       MENINGOCOCCUS  MENINGITIS 

disturbed  in  this  disease.  In  the  chronic  stage, 
forced  feeding  is  demanded  to  overcome  the  emacia- 
tion which  is  so  marked  a  feature  of  the  disease. 

To  carry  out  the  serum  treatment  under  the  best 
conditions,  it  is  desirable  that  the  patient  be  re- 
moved to  a  hospital.  The  chief  indication  for  the 
repetition  of  the  injections,  as  we  have  seen,  is  to  be 
found  in  the  examination  of  the  cerebrospinal  fluid. 
This  can  not  conveniently  be  carried  out  while  the 
patient  is  home. 

Careful  nursing  constitutes  an  important  part  of 
the  treatment.  For  very  restless  patients  the  bed 
should  be  well  padded  and  the  extremities  wrapped 
up  to  prevent  bruising.  The  danger  of  the  develop- 
ment of  bed-sores  is  to  be  guarded  against  by  cleanli- 
ness, local  use  of  alcohol  and  powder.  In  cases  with 
marked  retraction  of  the  head,  a  pad  should  be 
placed  beneath  the  occiput.  In  comatose  and 
apathetic  patients  we  must  watch  carefully  for 
urinary  retention.  Evacuation  of  the  bladder  by 
catheter  not  infrequently  is  necessary.  Retention 
may  be  present  despite  the  existence  of  incontinence. 

PROPHYLAXIS 

The  great  difficulties  to  be  overcome  in  the  carry- 
ing out  of  efficient  prophylactic  measures  against  the 
disease  are  best  realized  when  we  recall  some  of  the 


TREATMENT  301 

facts  that  have  been  established  regarding  the 
manner  of  its  transmission.  We  have  learned  that 
the  dissemination  of  the  disease  occurs  chiefly 
through  the  agency  of  healthy  germ  carriers.  Dur- 
ing an  epidemic  these  are  not  confined  to  the  imme- 
diate associates  of  each  patient,  but  are  generally 
diffused  throughout  the  community.  At  such 
periods  the  number  of  healthy  carriers  has  been 
estimated  by  Flugge  to  be  from  ten  to  twenty  times 
that  of  the  patients. 

To  check  the  spread  of  an  epidemic  in  a  locality 
would,  therefore,  require  the  detection  and  isolation 
of  all  germ  carriers  in  a  community,  a  task  mani- 
festly impossible  of  accomplishment.  But  even  if 
this  were  done  at  the  very  earliest  beginning  of  an 
outbreak,  the  time  necessarily  consumed  in  the  pro- 
cess of  isolation  of  the  meningococcus  from  the  naso- 
pharynx would  permit  of  the  diffusion  of  the  organ- 
ism beyond  the  confines  of  the  original  focus  of 
infection. 

Complete  isolation  of  all  those  who  come  in  close 
contact  with  the  patients  on  the  assumption  of  their 
being  possible  germ  carriers  can  not  well  be  carried 
out  for  economic  reasons.  The  infliction  of  such  a 
hardship  might  perhaps  be  justified  were  we  in 
possession  of  means  of  rapidly  destroying  the  menin- 
gococcus  in  the  nasopharynx.      But   it  can  not  be 


302       MENINGOCOCCUS  MENINGITIS 

asserted  that  any  of  the  local  measures  hitherto  em- 
ployed have  proved  measurably  efficacious. 

Pyocyanase,  which  was  introduced  by  Escherich 
and  used  with  apparent  success  by  Jehle,  exhibits 
a  solvent  action  on  the  meningococcus  in  vitro.  But 
this  action  is  greatly  reduced  when  it  is  added  to 
albuminous  solutions.  Moreover,  Haber  has  shown 
that  pyocyanase  loses  its  solvent  action  of  the  menin- 
gococcus when  marked  irritation  of  the  pharynx 
and  nose  is  present.  Recently  Wassermann  and 
Kolle  have  advised  the  insufflation  of  dried  anti- 
meningitis  serum.  In  eight  cases,  Kutscher  suc- 
ceeded by  this  method  in  rapidly  ridding  the 
nasopharynx  of  meningococci.  Vincent  advises 
inhalations  of  the  following  mixture: 

Iodine    20.00 

Guaiacol    2.00 

Thymic  acid 0.25 

Alcohol  (60  per  cent.) .  200.00 

A  small  quantity  of  this  mixture  is  put  in  a  porce- 
lain dish  which  is  then  placed  in  a  bowl  of  boiling 
water  to  aid  the  evaporation  of  the  mixture.  The 
vapors  are  inhaled  through  the  nose  four  or  five 
times  a  day  for  about  three  minutes.  The  inhalations 
are  supplemented  by  local  applications  twice  a  day 
of  iodo-glycerin   (1:30)   to  the  tonsil  and  pharynx. 


TREATMENT  303 

Gargling  or  rinsing  of  the  mouth  at  frequent  inter- 
vals with  diluted  peroxide  of  hydrogen  is  recom- 
mended. In  France  this  method  has  attained  con- 
siderable vogue  and  has  been  adopted  in  the  army 
regulations.  When  we  consider  the  protection 
afforded  the  meningococcus  by  the  numerous  folds 
of  the  mucous  membrane  of  the  nasopharynx,  it  does 
not  seem  likely  that  any  local  application,  whether 
in  the  form  of  inhalation  spray  or  insufflation,  will 
prove  effective  in  rapidly  destroying  all  the  menin- 
gococci in  this  region.  At  best  we  can  only  expect 
a  reduction  in  the  number  of  germs. 

In  view  of  these  facts,  we  must  content  ourselves 
with  the  adoption  of  those  practical  measures  which 
promise  merely  a  reduction  in  the  number  of  cases. 
All  cases  should  be  reported  to  the  local  health 
authorities.  In  the  interest  of  the  patient  and  the 
community,  it  is  advisable  to  remove  every  patient  to 
a  hospital.  Efficient  serum  treatment  demands  fre- 
quent laboratory  examination  of  the  cerebrospinal 
fluid,  and  this,  except  in  rare  cases,  can  not  well  be 
done  while  the  patient  remains  home.  The  well- 
known  rarity  of  germ  carriers  in  hospitals  renders 
the  spread  of  the  disease  from  these  institutions  very 
unlikely. 

If  the  patient  remains  at  home,  he  should  be 
isolated,  and  the  intercourse  between  the  members 


304       MENINGOCOCCUS  MENINGITIS 

of  the  family  and  the  outside  world  restricted  as 
much  as  possible.  The  secretions  of  the  nose  and 
throat,  the  urine,  and  the  stools  should  be  disin- 
fected as  in  typhoid  fever.  The  throat  should  be 
sprayed  several  times  a  day  with  V-i  per  cent,  per- 
oxide of  hydrogen.  The  bed  and  body  linen  should  be 
disinfected,  as  well  as  all  articles  which  are  likely  to 
be  soiled  with  nasopharyngeal  secretions.  For  dis- 
infection, 2%  per  cent,  carbolic  acid,  V2  per  cent, 
bichloride  of  mercury,  or  chloride  of  lime  may  be 
used. 

The  children  in  the  family  should  not  be  per- 
mitted to  visit  the  public  schools  for  at  least  three 
weeks.  Rarely  is  it  advisable  to  close  the  schools. 
In  severe  epidemics  large  public  gatherings  should 
not  be  permitted  by  the  health  authorities.  Young 
children  should  not  be  permitted  to  come  in  intimate 
contact  with  persons  coming  from  infected  localities. 

Prophylactic  Vaccination. — Sophian  and  Block, 
by  injecting  meningococcus  vaccines  in  eleven  stu- 
dents, demonstrated  the  appearance  in  the  blood  of 
agglutinins  and  antibodies.  Hall,  of  Kansas  City, 
gave  three  full  vaccinations  (500,  1000,  and  1000 
million  killed  bacteria)  to  280  individuals  of  50 
families  in  which  the  disease  occurred.  None  of  these 
subsequently  developed  the  disease.  In  Dallas, 
Texas,   about   100   persons   were  vaccinated.     Two 


\ 


TREATMENT  305 

nurses,  each  of  whom  had  two  injections,  developed 
the  disease  some  weeks  after  the  vaccinations.  Both 
of  them  recovered.  On  account  of  the  possible 
danger  of  developing  the  disease  during  the  negative 
phase,  it  is  advisable  to  make  cultures  of  the  nose 
and  throat  before  the  vaccination  is  done.  If  the 
meningococcus  is  found,  it  would  be  well  to  defer 
the  injections  until  the  organism  has  disappeared. 
On  the  other  hand,  in  a  number  of  instances  the 
vaccination  was  followed  by  the  disappearance  of  the 
organisms  within  a  week.  On  account  of  the 
naturally  slight  degree  of  susceptibility  to  the  dis- 
ease, it  will  require  many  thousands  of  vaccinations 
to  establish  the  prophylactic  value  of  this  mode  of 
treatment. 

Bibliography 

Flexner:    Jour.  Amer.  Med.  Assn.,  1906,  xlvii,  560. 
Jaeger:    Wien.  med.  Wochenschr.,  1906,  lvi,  2145. 
Jochmann :     Deut.  med.  Wochenschr.,  1906,  xxxii,  788. 
Ruppel:    Deut.  med.  Wochenschr.,  1906,  xxxii,  1366. 
Flexner:    Jour.  Exp.  Med.,  1907,  ix,  105. 
Jour.  Exp.  Med.,  1907,  ix,  168. 
Schoene:     Ther.  d.  Gegenwart,  1907,  xlviii,  52. 
Wassermann:     Deut.  med.  Wochenschr.,  1907,  xxxiii,  1585. 
Neufeld:     Med.  Klinik,  1908,  ii,  1341. 
Flexner  and  Jobling:    Jour.  Exp.  Med.,  1908,  x,  141. 

Jour.  Exp.  Med.,  1908,  x,  690. 
xdd:    Jour.  Amer.  Med.  Assn.,  1908,  lx,  1315. 
20 


306       MENINGOCOCCUS  MENINGITIS 

Robb:    Brit.  Med.  Jour.,  1908,  i,  382. 

Ker:    Edinb.  Med.  Jour.,  1908,  i,  306. 

Koplik:    Med.  Record,  1908,  lxxiv,  557. 

Dunn :     Boston  Med.  and  Surg.  Jour.,  1908,  1,  370. 

Sladen:    Jour.  Amer.  Med.  Assn.,  1908,  li,  1318. 

Churchill:    Jour.  Amer.  Med.  Assn.,  1908,  li,  21. 

Weiss-Eder:     Med.  Klinik,  1908,  iv,  1337. 

Holt:    Brit.  Med.  Jour.,  1908,  ii,  1336. 

Dopter:     Soc.  Med.  des  Hop.,  1909,  xxviii,  39. 

Holm:     Klin.  Jahrbuch,  1909,  xx,  357. 

Jehle:    Berl.  klin.  Wochenschr.,  1909,  xlvi,  899. 

Jobling:    Jour.  Exp.  Med.,  1909,  xi,  614. 

Selter:    Klin.  Jahrbuch,  1909,  xx,  457. 

Vincent  and  Bellot :    Bull,  et  Mem.  Soc.  Med.  de  Hop.,  1909. 

Fischer :    New  York  Med.  Jour.,  1910,  xci,  625. 

Dunn:     Defense  of  Research  Pamphlet,  Chicago,  1911,  xxi. 

Levy:      Serumbehandlung    der    epidemischen    Genickstarre, 

Jena,  1911. 
Debre:    Recherches  epidemiol.  clin.  et  therapeut.,  These  de 

Paris,  1911. 
Jochmann:    Deut.  med.  Wochenschr.,  1911,  xxxvii,  1733. 
Netter    and   Debre:     Le    Meningite    Cerebrospinal,    Paris, 

1911. 
Carnot  and  Marie:    Bull,  et  Mem.  Soc.  des  Hos.,  1911,  xxxi, 

74. 
Levy:    Arch.  f.  Kinderhk.,  1912,  lix,  72. 
Dopter:   Paris  Med.,  2,  1911-1912,  461. 
Sophian :    Jour.  Amer.  Med.  Assn.,  1912,  lviii,  843. 
Sophian  and  Black:    Jour.  Amer.  Med.  Assn.,  1912. 


TREATMENT  307 

Menetrier  and  Brodin :     Bull,  et  Mem.  Soc.  des  Hop.,  1912, 

xxxiii,  777. 
Haynes:     Trans.   Amer.   Laryngol.,  Rhinolog.   Soc,   1912, 

186. 
Widal  and  Weissenbach :     Bull,  de  l'Acad.  de  Med.,  Paris, 

1912,  lxviii,  81. 
Sophian :      Epidemic    Cerebrospinal    Meningitis,    St.    Louis, 

1913. 
Flexner:   Jour.  Exp.  Med.,  1913,  xvii,  553. 


INDEX 


Abortive  type.  104 
Age  incidence,  49 
Agglutination,  232 
Aggressins,  247 

Albumin,    increase   of,    in   cerebro- 
spinal fluid,  166 
Albuminuria,  141 
Amboceptors,  specific,  247 
Animal  inoculation,  232 
Anti-endotoxins,  253 
Appearance  and  attitude,  125 
Arthropathy,  188,  209 
treatment  of,  297 
Aural  complications,  183-187 
clinical  course,  186 
deafness,  183 

associated  with  mut- 
ism, 184 
frequency  of,  184 
otitis  media,  183 
pathological  anatomy  and 
pathogenesis,  185,  186 
route  of  invasion,  72 

B 

Babinski  reflex,  130 
Bactericidal  bodies,  235 
Bacteriology,  12 
Bacteriolysins,  253 
Bacteriotropins,  253 
Bed-sores,  102 
Biot  type  of  respiration,  124 
Blindness,     occurrence    in    serum- 
treated  cases,  287 
Blood,  232-236 

cultures,  74,  189,  235 

picture,  142,  143 

pressure,  143,  260 
Bonhoff  and  Lepierre,  serum  of,  246 
Braun  and  Ilnsler  test,  226 
Brudzinski's  sign,  135,  209 
Bulging  of  anterior  fontanelle,  107, 
120,  137,  138,  209 

of  posterior  fontanelle,  138 


Cardiac  complications,  192 

Carphologia,  129 

Carriers,    57,    59,    61,    63,    64,    66, 

69 
Catalepsy,  174 
Catarrhal  conditions  of  nasopharynx, 

influence  of,  51,  55 
Causes  of  epidemics,  69,  76 
Cerebrospinal     fluid,     complement 
and  complement  fixation 
in,  231 
cytology  of,  228 
etiological    diagnosis     by, 

224 
in   meningococcus   menin- 
gitis, 163-172 
normal,  162,  225 
Cheyne-Stokes  respiration,  101,  103. 

123 
Cisterna  magna,  197 
Clinical  types,  97-105 
Coma,  125 

Complement  fixation,  235 
Complications,  173-195 
Condition  of  the  patient  predispos- 
ing, 51 
Contagiousness,  43-47 
Contralateral  reflex,  135,  136 
Controversy  as  to  causative  organ- 
ism, 15,  16 
Convalescence,  144 
Convulsions,  102,  103,  129,  208 
Cranial  nerve  complications,  171 
Crohn's  apparatus,  154 
Cystitis,  193 

D 

Deafness,     occurrence     in     serum- 
treated  cases,  287 
Definition,  1 
Delirium,  125,  174,  20S 
Delusions,  1 7  I 
Diagnosis,  207-2 12 

sourct'8  of  error  in,  209,  210 
309 


310 


INDEX 


Diagnosis,   differential  from;  acute 
suppurative   meningitis, 
220 
aseptic  meningitis,  220 
gastro-enteritis,  218 
infantile  eclampsia,  219 
influenza,  215 
meningism,  217 
meningeal  hemorrhage, 

218 
pneumonia,  213 
polioencephalitis,  217 
poliomyelitis,  216 
septicopyaemia,  215 
tetanus,  215 
tetany,  219 
tuberculous  meningitis, 

220 
typhoid  fever,  213 
typhus  fever,  214 
Dopter's  serum,  250,  251 
Dosage  of  serum,  273 
Dry  taps  in  posterior  basic  menin- 
gitis, 114,  164 

E 

Effects  of  serotherapy  on: 
blood-pressure,  261 
cerebrospinal  fluid,  283 
complications  and  sequelae, 

286 
cytology,  283 
duration  of  disease,  285 
macroscopic  appearance  of 

fluid,  283 
meningococci,  284 
mortality,  275-281 
protein   contents  of   cere- 
brospinal fluid,  283 
relapses,  285 
symptoms,  281 
Emaciation,  102,  114,  131 
Enzymes,  intracellular,  248 
Epidemics,  5,  6,  7 
Epidemiology,  42,  43 
Epididymitis,  193 
Eruption,  morbilliform,  140 
purpuric,  141,  142 
roseolar,  140 
scarlatinaform,  140 
Erythema,  131,  141,  209 
Eustachian  tubes,  72 


Fast  cases,  292,  293 
Fibrin  in  cerebrospinal  fluid,  225 
Flexner  and  Jobling,  250,  255 
Flexner  serum,  248,  250 
Frequency  of  serum  injections,  263 
Fulminating  type,  103 

in  infancy,  106 
Furunculosis,  193 

G 

Gastro-intestinal  disturbances,  138 
139,  192 
tract,  lesions  in,  93 
Geographic  distribution,  47 

H 

Haematuria,  142 
Hallucinations,  174 
Headache,  118,  119,  128,  208 
Healthy  carriers,  64,  66-69 
Heart  lesions,  93 
Hemiplegia,  176 
Herpes,  100,  139,  140,  209 
Hippus,  100 
History,  2 

of  treatment,  243 
Hydrocephalus,  acute,  201 

chronic,  102,  138,  173,  197 

internal,  197-206 

pathological  anatomy  and  path- 
ogenesis of,  197 
Hygienic  conditions  influencing  oc- 
currence, 51 
Hyperacute  type,  104 
Hyperesthesia,  99, 107, 128, 178,  208 

relief  of,  by  lumbar  puncture, 
129 


Icterus,  192 

Incontinence  of  urine,  193 
Incubation  period,  duration  of,  98 
Infancy,  meningococcus  meningitis 

in,  106-116 
Insomnia,  125 
Intermittent  type,  104,  105 
Intracranial,    intrapharyngeal,    and 

intravenous  inoculation,  74 
Invasion,  symptoms  of,  98 
Isolation,  303 


INDEX 


311 


Jaeger  and  specific  agglutinins,  246 
Jochmann's  serum,  245,  251 


Kernig  sign,  99,  108,  114,  133-135, 

209 
Kidneys,  acute  degeneration  of,  94 
Kolle  and  Wassermann,  serum  of, 

245,  251 
Koplik,  studies  on  posterior  basic 
meningitis,  111 
on  hydrocephalus  complicating 
meningococcus      meningitis, 
200 
prostration  at  onset  distinguish- 
ing   from    polioencephalitis, 
217 
Krcenig's  apparatus,  154,  155 


Laboratory  diagnosis,  224-236 
Lesions,     macroscopic,     of    central 
nervous  system  in  acute 
stage,  81-84 
in  chronic  stage,  84,  85 
microscopic,  in  acute  stage,  85- 
89 

in  chronic  stages,  89-91 
Leucocytosis,  109,  114,  142 
Liver,  192 

Lumbar  puncture,  anatomical  con- 
siderations    and     land- 
marks, 148,  152 
exact  etiological  diagnosis 

by,  148 
in  hydrocephalus,  295 
instruments  for,  152 
preparations  for,  155,  156 
relieves  hyperesthesia,  129 
technic  of,  156-160 
Luschka,  foramina  of,  197,  198 

M 

Macewen's  sign,  108,  120,  138,  209 
Majendie,   obliteration  of  foramen 

of,  97,  198 
Miliaria,  simulation  of,  105,  211 
Marasmus,  102 
Medfield,  Mass.,  epidemic  in,  3 


Meningococcus,  absorption  tests  on, 
29 
action  of  bile  salts  on,  30 
on  dogs,  33 
on  goats,  34 
on  guinea-pigs,  32 
on  monkeys,  34 
on  rabbits,  33 
agglutination  of,  27-29 
complement   fixation   reaction, 

30 
conditions    affecting    viability 

of,  23-25 
cultural  characteristics  of,  19-23 
difference  in  strains  of,  35 
discovery  of  by  Weichselbaum, 

12,  13 
effect  of  intraspinal  injections 

of,  34 
influenced  by  serum  injections, 

284 
intravenous  reaction,  31 
mode  of  invasion  of  meninges 

by,  71-76 
morphology  of,  17 
pathogenicity  of,  32 
peritoneal  reaction,  30,  31,  116 
polymorphism  of,  18 
peritoneal  reaction,  30,  116 
presence  in  cerebrospinal  fluid, 

165 
staining  of,  16,  166 
by  Gram,  229 
Mental  condition,  125 
Mentality,  impaired  in  serum- 
treated  cases,  287 
Mild  type,  104 
Moritz  test,  225 

Morphologv  of  meningococcus,  17 
Mortality,  237 

in  epidemics,  238 
influenced  by  serotherapy,  275- 
281 
Motor  disturbances,  129 
Mydriasis  on  flexion  of  the  head  or 

'irritation  of  the  skin,  208,  209 
Myocardium,  lesions  in,  93 

N 

Nasopharynx    harboring    meningo- 
cocci, 55,  57,  60,  62,  63,  65,  236 
Nephritis,  141,  193 


312 


INDEX 


Nervous  system,    complications  of 
meningitis   involving, 
174-178 
demonstration  of  the  men- 
ingococcus in,  91 
lesions  in,  81-91 
Noguchi  test,  226 
Nonne  and  Apelt's  test,  225 
Nystagmus,  127 

O 

Ocular  complications,  178-183 
amaurosis,  182,  183 
conjunctival  hemorrhages, 

ISO 
conjunctivitis,  179,  180 
iridocyclitis,  180 
keratitis,  180 
orbital  cellulitis,  181 
panophthalmus,  181 
symptoms,  126,  127,  179,  etc. 

Onset,  mode  of,  118 

symptoms  of,  98,  119 

Opisthotonus,  129,  136,  208 

Oppenheim  reflex,  130 

Opsonic  index,  234 

Optic  nerve,  changes  in,  127,  183 

Ordinary  type,  97 

in  infancy,  106 

Orthotonus,  208 

Overcrowding,  influence  of,  51,  61 


Papillitis,  128 

Paralyses  complicating  meningitis, 
174-176 
frequency  of,  175 
occurrence     in     serum-treated 
cases,  287 
Pathogenesis,  117,  118 
Pathologic  anatomy,  78-95 
Periods  in  the  history  of  meningo- 
coccus meningitis,  6-10 
Petechia;  in  skin,  100,  103,  141,  209 
in  mucous  membrane  of  stom- 
ach and  intestines,  93 
Poliomyelitis,  mode  of  invasion  of 

virus  probably  similar  in,  73 
Posterior  basic  meningitis,  110,  111 
clinical  course  of,  111, 
112 


Posterior  basic  meningitis,  identity 
of,  with  meningo- 
coccus meningitis, 
115,  116 
pathologic  anatomy 
of,  111,  112 
Precipito-reaction   of   Vincent   and 

Bellot,  230 
Prognosis,  237-242 

age  incidence  affecting,  239 
as  to  complete  recovery,  241 
early  diagnosis  affecting,  240 
factors  in,  239 

gravity  of  symptoms  influenc- 
ing, 240 
serum    treatment    influencing, 
240 
Prophylaxis,  300 

cleanliness  of  mouth  and  nose, 

302 
insufflation  of  dried  serum  in, 

302 
isolation,  304 
pyocyanase  in,  301 
vaccination,  303 
Protein    content    of    cerebrospinal 

fluid,  225 
Psychic  disturbances,  193 
Pulse,  122,  20S 

Pupillary  reactions,  99,  126,  208 
Pupils,  inequality  of,  126 

dilatation  of,  127 
Pyelitis,  absence  of,  193 

Q 

Quincke    needle    and    manometer, 
152-154 

R 

Race  incidence,  50 
Recrudescences,  266 
Reflexes,  129,  130,  176 
Relapses,  143,  144,  239 
Respirations,  123,  124,  208 
Respiratory  complications,  188,  189 
tract,  distribution  of  meningo- 
cocci in,  64 
lesions  in,  92 
Restlessness,  99,  108,  125,  131,  132, 

208 
Retention  of  urine,  193 
Retraction  of  head,  137,  208 


INDEX 


:13 


Rigidity  of  neck,  98,  107,  208 

of  spine,  99,  208 
Ruppel,  serum  of,  252 

S 

Seasonal  incidence,  47 
Sequelae,  193-195 
Sensory  disturbances,  128 
Serotherapy,  basic  principles  of,  255 
causes  of  failure  with,  292 
dosage,  273 
in  complications,  272 
intra  ventricular  injection,  268- 

270 
results  of,  274 
routine  treatment,  262 
technie,  258 
Serum,    antimeningitis,    absorption 
of,  257 
antiproteolytic  ferment  in, 

257 
elimination  of,  257 
manner  of  therapeutic  ac- 
tion of,  252 
polyvalency  of,  252 
preparation,  250 
standardization  of,  254 
disease,  288 

treatment  of,  297 
Sex  incidence,  50 
Skin,  lesions  in,  95 
Sodium  faurocholate  test,  232 
Sophian  method  of  controlling  in- 
jection by  the  blood-pressure,  260, 
261 
Source   of   meningococci    in    naso- 
pharynx. 65 
Sphenoidal  sinuses,  invasion  of,  by 

meningococci,  71 
Spleen,  192 
Sporadic  eases.  52,  53 
Staining,  16 
Status  epilepticus,  129 
Strabismus,  127,  174.  208 
Subsultus  tendinum,  129 
Sugar  in  cerebrospinal  fluid,  166  167 


Susceptibility  to  infection,  46 
Symptomatology,  117-145 

of   fluid   obtained   by   lumbar 
puncture,  table  facing  224 
Synonyms,  1,  139 

T 

Tache  cerebrale,  100,  114,  130,  208 
Temperature,  critical  fall  in,  144 

fall   of,   after  serum  injection, 
122 

indefinite  type  of,  120 

intermittent,  121 

remittent,  121 

subnormal,  102 
Terminology,  1 
Treatment,  243-305 

by  lumbar  puncture,  295 

general  management,  298 

history  of,  243 

hot  baths,  296 

passive  hyperemia,  296 

surgical  procedures,  298 

symptomatic,  294 
Trans-etlimoidal  route  of  invasion, 

72 
Tremor  of  hands,  129 
Trophic  disturbances,  130 

D 

Untoward   results   from   serum   ad- 
ministration, 290 


Vaccination,  prophylactic,  304 
Vasomotor  disturbances,  130 
Vesiculitis,  193 

Visceral  complications,  187,  188 
Vomiting,  lis.  119,  192,  208 

W 

Weichselbaum,   discovery  of   men- 
ingococcus by,  12,  13 


DATE  DUE 


Demco, 


Inc.  38-293 


854307351 A 


RCl^ 
H36 
Heiraan  1913 

Meningococcus  meningitis. 


